Triclosan Decreases Rat Thyroxine: Mode-of-Action, Developmental Susceptibility and Human Relevance

EPA Science Inventory

Triclosan (TCS) decreases serum thyroxine (T4) in the rat. In vivo and in vitro approaches were used to address three uncertainties: by what mode-of-action (MOA) does TCS decrease T4; does TCS decrease T4 developmentally; and, are effects observed in rats relevant to humans? To t...

Circulating thyroid hormones and associated metabolites in white whales (Delphinapterus leucas) determined using isotope-dilution mass spectrometry.

PubMed

Hansen, Martin; Villanger, Gro D; Bechshoft, Thea; Levin, Milton; Routti, Heli; Kovacs, Kit M; Lydersen, Christian

2017-07-01

Blood was sampled from nine free-ranging white whales (beluga whale, Delphinapterus leucas) from Svalbard, Norway during the summers of 2013 and 2014. Total concentrations of eleven thyroid hormones and metabolites were measured in serum using a novel liquid chromatography tandem mass spectrometry analytical method. Measurements of these compounds in plasma gave the same results as in serum. The three hormones found in highest concentrations were 3,3',5-triiodothyronine (T 3 ), 3,3',5'-triiodothyronine (rT 3 ) and thyroxine (T 4 ). Traces of associated metabolites were also found. Copyright © 2017 Elsevier Inc. All rights reserved.

A Common Variation in Deiodinase 1 Gene DIO1 Is Associated with the Relative Levels of Free Thyroxine and Triiodothyronine

PubMed Central

Panicker, Vijay; Cluett, Christie; Shields, Beverley; Murray, Anna; Parnell, Kirstie S.; Perry, John R. B.; Weedon, Michael N.; Singleton, Andrew; Hernandez, Dena; Evans, Jonathan; Durant, Claire; Ferrucci, Luigi; Melzer, David; Saravanan, Ponnusamy; Visser, Theo J.; Ceresini, Graziano; Hattersley, Andrew T.; Vaidya, Bijay; Dayan, Colin M.; Frayling, Timothy M.

2008-01-01

Introduction: Genetic factors influence circulating thyroid hormone levels, but the common gene variants involved have not been conclusively identified. The genes encoding the iodothyronine deiodinases are good candidates because they alter the balance of thyroid hormones. We aimed to thoroughly examine the role of common variation across the three deiodinase genes in relation to thyroid hormones. Methods: We used HapMap data to select single-nucleotide polymorphisms (SNPs) that captured a large proportion of the common genetic variation across the three deiodinase genes. We analyzed these initially in a cohort of 552 people on T4 replacement. Suggestive findings were taken forward into three additional studies in people not on T4 (total n = 2513) and metaanalyzed for confirmation. Results: A SNP in the DIO1 gene, rs2235544, was associated with the free T3 to free T4 ratio with genome-wide levels of significance (P = 3.6 × 10−13). The C-allele of this SNP was associated with increased deiodinase 1 (D1) function with resulting increase in free T3/T4 ratio and free T3 and decrease in free T4 and rT3. There was no effect on serum TSH levels. None of the SNPs in the genes coding for D2 or D3 had any influence on hormone levels. Conclusions: This study provides convincing evidence that common genetic variation in DIO1 alters deiodinase function, resulting in an alteration in the balance of circulating free T3 to free T4. This should prove a valuable tool to assess the relative effects of circulating free T3 vs. free T4 on a wide range of biological parameters. PMID:18492748

A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine.

PubMed

Panicker, Vijay; Cluett, Christie; Shields, Beverley; Murray, Anna; Parnell, Kirstie S; Perry, John R B; Weedon, Michael N; Singleton, Andrew; Hernandez, Dena; Evans, Jonathan; Durant, Claire; Ferrucci, Luigi; Melzer, David; Saravanan, Ponnusamy; Visser, Theo J; Ceresini, Graziano; Hattersley, Andrew T; Vaidya, Bijay; Dayan, Colin M; Frayling, Timothy M

2008-08-01

Genetic factors influence circulating thyroid hormone levels, but the common gene variants involved have not been conclusively identified. The genes encoding the iodothyronine deiodinases are good candidates because they alter the balance of thyroid hormones. We aimed to thoroughly examine the role of common variation across the three deiodinase genes in relation to thyroid hormones. We used HapMap data to select single-nucleotide polymorphisms (SNPs) that captured a large proportion of the common genetic variation across the three deiodinase genes. We analyzed these initially in a cohort of 552 people on T(4) replacement. Suggestive findings were taken forward into three additional studies in people not on T(4) (total n = 2513) and metaanalyzed for confirmation. A SNP in the DIO1 gene, rs2235544, was associated with the free T(3) to free T(4) ratio with genome-wide levels of significance (P = 3.6 x 10(-13)). The C-allele of this SNP was associated with increased deiodinase 1 (D1) function with resulting increase in free T(3)/T(4) ratio and free T(3) and decrease in free T(4) and rT(3). There was no effect on serum TSH levels. None of the SNPs in the genes coding for D2 or D3 had any influence on hormone levels. This study provides convincing evidence that common genetic variation in DIO1 alters deiodinase function, resulting in an alteration in the balance of circulating free T(3) to free T(4). This should prove a valuable tool to assess the relative effects of circulating free T(3) vs. free T(4) on a wide range of biological parameters.

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.

THYROXINE (T4) CATABOLISM IN HUMAN AND RAT HEPATOCYTES INCREASES FOLLOWING EXPOSURE TO HEPATIC ENZYME INDUCERS

EPA Science Inventory

Nuclear receptor agonists phenobarbital (PB), 3-methylcholanthrene (3MC), pregnenolone-16a-carbonitrile (PCN), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and 2,2' ,4,4'-tetrabromodiphenyl ether (BDE 47) decrease serum thyroxine (T4) in rats. This decrease is thought to occur th...

PCB-153 AND BDE-47 INCREASE THYROXINE T4) CATABOLISM IN RAT AND HUMAN HEPATOCYTES

EPA Science Inventory

Previous studies demonstrate that in vivo exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) decrease serum thyroxine (T4) levels in rats. This decrease is thought to occur through the induction of hepatic metabolizing enzymes ...

HEPATIC ENZYME INDUCERS INCREASE THYROXINE (T4) CATABOLISM IN HUMAN AND RAT HEPATOCYTES

EPA Science Inventory

Nuclear receptor agonists such as 3-methylcholantrene (3-MC), phenobarbital (PB), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and, pregnenolone-16a-carbonitrile (PCN) decrease serum thyroxine (T4) concentrations in rats. It appears that this decrease occurs through the induction...

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.

RELATIONSHIP BETWEEN HEPATIC MICROSOMAL THYROXINE GLUCURONIDATION AND TOTAL SERUM THYROXINE CONCENTRATIONS IN RATS TREATED WITH PCDDS, PCDFS AND PCBS

EPA Science Inventory

RELATIONSHIP BETWEEN HEPATIC MICROSOMAL THYROXINE GLUCURONIDATION AND TOTAL SERUM THYROXINE CONCENTRATIONS IN RATS TREATED WITH PCDDs, PCDFs AND PCBs. D G Ross, K M Crofton, M J DeVito, NHEERL, ORD, USEPA, RTP, NC.
Many PHAHs decrease thyroxine (T4), possibly due to inducti...

Clinical assessment of a radioimmunoassay for free thyroxine using a modified tracer

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

Chan, D.W.; Waud, J.M.; Hsu, T.H.

1983-06-01

A radioimmunoassay for measuring free thyroxine in plasma was introduced by Amersham using a I-125-labeled T4 derivative that does not bind significantly to the thyroxine-binding proteins. We evaluated this RIA for its clinical utility in assessing 278 patients with thyroid and nonthyroidal diseases. The precision of the Amerlex free T4 assay, expressed as coefficient of variation, was 20% at 0.16 ng/dl, 6.9% at 0.55 ng/dl, 4.2% at 1.08 ng/dl, 5.3% at 2.29 ng/dl, and 6.3% at 3.18 ng/dl. A reference range for free T4 was established as 0.68-1.8 ng/dl, n . 171. The correlation coefficients (r) of a dialysis methodmore » and a free thyroxine index were 0.871 and 0.911, respectively. Free T4 correctly classified 98% euthyroid, 92% hypothyroid, 100% hyperthyroid, 100% euthyroid with elevated TBG, and 87% of phenytoin patients. In addition, 80 patients with acute nonthyroidal illness were studied. Most of these patients have normal to low free T4, very low T3, and elevated rT3. We found this free T4 assay to be precise, easy to perform, and reliable in classifying thyroid status in most patients.« less

THYROXINE (T4) CATABOLISM IN HUMAN AND RAT HEPATOCYTES INCREASES FOLLOWING EXPOSURE TO PROTOTYPICAL HEPATIC ENZYME INDUCERS

EPA Science Inventory

Nuclear receptor agonists such as phenobarbital (PB), 3-methylcholantrene (3MC), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and, pregnenolone-16a-carbonitrile (PCN) decrease serum thyroxine (T4) concentrations in rats. This decrease is thought to occur through the induction of ...

Biosensor discovery of thyroxine transport disrupting chemicals

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

Marchesini, Gerardo R.; Meimaridou, Anastasia; Haasnoot, Willem

2008-10-01

Ubiquitous chemicals may interfere with the thyroid system that is essential in the development and physiology of vertebrates. We applied a surface plasmon resonance (SPR) biosensor-based screening method for the fast screening of chemicals with thyroxine (T4) transport disrupting activity. Two inhibition assays using the main thyroid hormone transport proteins, T4 binding globulin (TBG) and transthyretin (TTR), in combination with a T4-coated biosensor chip were optimized and automated for screening chemical libraries. The transport protein-based biosensor assays were rapid, high throughput and bioeffect-related. A library of 62 chemicals including the natural hormones, polychlorinated biphenyls (PCBs), polybrominated diphenylethers (PBDEs) and metabolites,more » halogenated bisphenol A (BPA), halogenated phenols, pharmaceuticals, pesticides and other potential environmentally relevant chemicals was tested with the two assays. We discovered ten new active compounds with moderate to high affinity for TBG with the TBG assay. Strikingly, the most potent binding was observed with hydroxylated metabolites of the brominated diphenyl ethers (BDEs) BDE 47, BDE 49 and BDE 99, that are commonly found in human plasma. The TTR assay confirmed the activity of previously identified hydroxylated metabolites of PCBs and PBDEs, halogenated BPA and genistein. These results show that the hydroxylated metabolites of the ubiquitous PBDEs not only target the T4 transport at the TTR level, but also, and to a great extent, at the TBG level where most of the T4 in humans is circulating. The optimized SPR biosensor-based transport protein assay is a suitable method for high throughput screening of large libraries for potential thyroid hormone disrupting compounds.« less

[Iodine deficiency and pregnancy].

PubMed

Trimarchi, F; Lo Presti, V P; Vermiglio, F

1998-01-01

Iodine availability for maternal thyroid during pregnancy results from a combination of specific factors (increased urinary iodine loss, fetal-placental unit competition) and is critically reduced by the nutritional deficiency. Hyperestrogenism is associated with increased circulating thyroxine-binding globulin (TBG) levels and a higher binding capacity for T4 and T3, because of a reduced clearance rate of the protein. Our study carried out in a moderately iodine deficiency area from North-Eastern Sicily in pregnant women showed a inadequate synthesis of T4 not proportional to the increased TBG levels. The progressive decrease T4/TBG molar ratio implies the reduction of serum FT4 and the consequently increase of serum TSH. At delivery, about 70% of women showed a critical and transient biochemical hypothyroidism. Mental impairment and neurosensorial and neuromuscular disorders were observed in children born from those women. Therefore, short-term iodine prophylaxis with iodized salt in pregnant women does not correct nor prevent maternal hypothyroxinemia. L-T4 treatment is thus often required.

In Vitro Metabolism of Thyroxine by Rat and Human Hepatocytes

EPA Science Inventory

The liver metabolizes thyroxine (T4) through two major pathways: deiodination and conjugation. Rodents utilize both pathways, but it is uncertain to what degree different species employ deiodination and conjugation in the metabolism of T4. The objective of this study was to compa...

Liquid L-thyroxine versus tablet L-thyroxine in patients on L- thyroxine replacement or suppressive therapy: a meta-analysis.

PubMed

Laurent, Irakoze; Tang, Siying; Astère, Manirakiza; Wang, Kan Ran; Deng, Shuhua; Xiao, Ling; Li, Qi Fu

2018-03-23

To compare the effectiveness of liquid L-T4 (L-thyroxine) and tablet L-T4 in patients on L-T4 replacement or suppressive therapy. The Cochrane Library, PubMed, Embase, and Web of Science databases were searched to identify relevant articles. All prospective or randomized controlled studies (RCTs) comparing liquid L-T4 and tablet L-T4 in patients on L-T4 replacement or suppressive therapy were included in the analysis. Overall, the initial search of the four databases identified 1278 published studies; of these, eight studies were ultimately included in the meta-analysis. TSH (thyroid stimulating hormone) levels were significantly suppressed in patients on liquid L-T4 compared with those on tablet L-T4, in patients on L-T4 suppressive therapy with L-T4 malabsorption (Mean Difference (MD) = -2.26, 95% Confidence Interval (CI): -3.59, -0.93; P = 0.0009)). However, liquid L-T4 and tablet L-T4 did not show a statistically significant difference in patients on L-T4 suppressive therapy without malabsorption (MD = 0.08, 95% CI: -0.31, 0.47; P = 0.69). TSH levels were significantly normalized in patients on liquid L-T4 compared with those on tablet L-T4, in Patients on L-T4 replacement therapy with L-T4 malabsorption (MD = -3.20, 95% CI: -5.08, -1.32; P = 0.0009). However, liquid L-T4 and tablet L-T4 did not show a statistically significant difference in patients on L-T4 replacement therapy without malabsorption (MD = 0.91, 95% CI: -0.03, 1.86; P = 0.06). Liquid L-T4 is more efficient than tablet L-T4 in patients on L-T4 replacement or suppressive therapy with malabsorption. No significant differences were observed in patients without malabsorption. Further studies should be conducted to verify these findings.

The influence of natural short photoperiodic and temperature conditions on plasma thyroid hormones and cholesterol in male Syrian hamsters

NASA Astrophysics Data System (ADS)

Vaughan, M. K.; Brainard, G. C.; Reiter, R. J.

1984-09-01

Adult male Syrian hamsters were subjected to 1, 3, 5, 7 or 11 weeks of either natural winter conditions or rigorously controlled laboratory conditions (LD 10∶14; 22 ± 2‡C). Although both groups of hamsters gained weight over the course of the experiment, hamsters housed indoors were significantly heavier after 5 weeks of treatment compared to their outdoors counterparts. Animals housed under natural conditions exhibited a significant decrease in circulating levels of thyroxine (T4) and a rapid rise in triiodothyronine (T3) levels; the free T4 and free T3 index (FT4I and FT3I) mirrored the changes in circulating levels of the respective hormones. Laboratory-housed animals had a slight rise in T4 and FT4I at 3 weeks followed by a slow steady decline in these values; T3 and FT3I values did not change remarkably in these animals. Plasma cholesterol declined steadily over the course of the experiment in laboratory-maintained animals but increased slightly during the first 5 weeks in animals under natural conditions. Since the photoperiodic conditions were approximately of the same duration in these 2 groups, it is concluded that the major differences in body weight, thyroid hormone values and plasma cholesterol are due to some component (possibly temperature) in the natural environment.

Thyroxine-Based Screening for Congenital Hypothyroidism in Neonates with Down Syndrome.

PubMed

Erlichman, Ira; Mimouni, Francis B; Erlichman, Matityahu; Schimmel, Michael S

2016-06-01

To ascertain whether thyroxine (T4)-based screening programs for congenital hypothyroidism (initial measurement of total T4 [tT4] followed by thyroid stimulating hormone [TSH] measurement in patients with tT4 <10th percentile) identifies congenital hypothyroidism in all neonates with Down syndrome. Retrospective cohort study of 159 neonates with Down syndrome, born during the period 1998-2007 were included. Screening test results were compared with those of the general population. All primary care physicians of these infants were contacted and infants' thyroid status verified. tT4 concentrations in children with Down syndrome were significantly lower, and TSH higher than those in the general population; tT4 concentrations did not correlate with screening TSH concentrations. Twenty children with Down syndrome were treated with L-thyroxin within the first month of life although only 10 babies had been identified by the routine screening test. T4-based screening does not identify many cases of congenital hypothyroidism in neonates with Down syndrome. We recommend that neonates with Down syndrome be screened by simultaneous measurements of both tT4 and TSH. Copyright © 2016 Elsevier Inc. All rights reserved.

Euthyroid ''thyroxine toxicosis''

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

Mankikar, G.D.; Clark, A.N.

A survey was made of thyroid function tests on 1,153 patients screened for thyroid disease during a two-year period in a Geriatric Department; 13 percent of the test results fell outside the normal range. Of 88 patients who showed above-normal results, only 12 presented with clinical features of thyrotoxicosis. In 37 patients, the biochemical findings indicated euthyroid ''thyroxine toxicosis''; high values were found for serum thyroxine (T4) and the free thyroxine index (FT4I) but there were no clinical signs or symptoms of thyrotoxicosis; the values reverted to normal within one to three weeks. This pattern was seen also in 7more » examples of T4-treated hypothyroidism. (Overall, the test findings indicated 61 cases of hypothyroidism.) The significance of this transient increase in T4 and FT4I values is discussed. The false positive results suggest that, when laboratory findings are not compatible with the clinical signs, the thyroid function tests should be repeated after another two weeks.« less

Adjunctive cholestyramine therapy for thyrotoxicosis.

PubMed

Solomon, B L; Wartofsky, L; Burman, K D

1993-01-01

Initial therapy of thyrotoxicosis usually includes beta-blockade for symptom relief and thionamides to block new thyroid hormone synthesis. In view of the increased enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) in thyrotoxicosis, we proposed that cholestyramine, an anion exchange resin which binds iodothyronines, when used adjunctively with thionamides and a beta-blocker, would lower serum iodothyronine levels faster than would standard therapy alone. A double blind placebo-controlled cross-over design was used with patients randomly assigned to either the treatment or control groups. They received their initial treatment for two weeks (Phase 1) followed by a one-week washout period, and then crossed to the opposite treatment for two weeks (Phase 2). Standard therapy included atenolol 50 mg daily, individualized dosages of methimazole and either 4 g of cholestyramine or 4 g of placebo powder four times per day. Fifteen patients with thyrotoxicosis (14 Graves' disease, 1 toxic adenoma) participated in this study. Total and free thyroxine and triiodothyronine, as well as thyroid-stimulating immunoglobulin and thyrotrophin-binding inhibitory immunoglobulin, were measured weekly. Seven patients received cholestyramine and eight patients received placebo during Phase 1. A more rapid decline in all thyroid hormone levels was seen in the cholestyramine-treated group (F = 4-7, P < 0.01) than in the placebo group (F = 2-3.1, P = 0.05). In Phase 2, the eight patients who received cholestyramine showed an additional decline in free thyroxine from weeks one to two, but the overall rate of decline in hormone levels was not different between the groups. Immunoglobulin levels remained unaffected regardless of group, treatment, or time. We conclude that cholestyramine is a safe and effective adjunctive agent in the treatment of thyrotoxicosis and that its greatest efficacy may be during the first few weeks of treatment.

Thyroxine transfer from cerebrospinal fluid into choroid plexus and brain is affected by brefeldin A, low sodium, BCH, and phloretin, in ventriculo-cisternal perfused rabbits.

PubMed

Zibara, Kazem; El-Zein, Ali; Joumaa, Wissam; El-Sayyad, Mohammad; Mondello, Stefania; Kassem, Nouhad

2015-01-01

Thyroxine (T4) hormone is synthesized by the thyroid gland and then released into the systemic circulation where it binds to a number of proteins. Dysfunction in T4 transport mechanisms has been demonstrated in multiple central nervous system (CNS) diseases including Alzheimer's disease. In the presence of different compounds that inhibit potential T4 transport mechanisms, this study investigated the transfer of T4 from cerebrospinal fluid (CSF) into Choroid Plexus (CP) and other brain tissues. The compounds used were brefeldin A, low sodium artificial CSF (aCSF), BCH, phloretin, and taurocholate (TA). Radiolabeled T4 ((125)I-T4) was perfused continuously into the CSF and was assessed in several brain compartments with reference molecule (14)C-mannitol and blue dextran, using the in vivo ventriculo-cisternal perfusion (V-C) technique in the rabbit. The aCSF containing the drug of interest was infused after 1 h of perfusion. Drugs were applied independently to the aCSF after 1 h of control perfusion. Of interest, in presence of low sodium or BCH, the percentage recovery of (125)I-T4, was increased compared to controls, with concomitant increase in T4 clearance. Conversely, brefeldin A, phloretin, and TA did not exert any significant effect on the recovery and clearance of (125)I-T4 assessed in aCSF. On the other hand, the uptake of (125)I-T4 into CP was raised by 18 fold compared to controls in the presence of brefeldin A. In addition, low sodium, BCH, or phloretin alone, enhanced the uptake of (125)I-T4 by almost 3-fold, whereas TA did not show any significant effect. Finally, the uptake and distribution of (125)I-T4 into other brain regions including ependymal region (ER) and caudate putamen (CAP) were significantly higher than in controls. Our study suggests the involvement of different mechanisms for the transfer of (125)I-T4 from CSF into CP and other brain regions. This transfer may implicate sodium-dependent mechanisms, amino acid "L" system, or organic anion transporting polypeptide (OATP).

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

PubMed

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

2018-04-01

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

TEMPORAL AND SPATIAL VARIATION IN PLASMA THYROXINE (T4) CONCENTRATIONS IN JUVENILE ALLIGATORS COLLECTED FROM LAKE OKEECHOBEE AND THE NORTHERN EVERGLADES, FLORIDA, USA

EPA Science Inventory

We examined variation in plasma thyroxine (T4) in juvenile American alligators (Alligator mississippiensis) collected from three sites within the Kissimmee River drainage basin (FL, USA). Based on historical sediment data, Moonshine Bay served as the low contaminant exposure site...

BDE 47 AND PCB 153 INCREASE THYROXINE CATABOLISM IN PRIMARY RAT AND HUMAN HEPATOCYTES: THE UTILITY OF HEPATOCYTES AS SCREENING TOOLS FOR POTENTIAL THYROID HORMONE DISRUPTORS

EPA Science Inventory

Studies demonstrate that exposure to 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) and 2,2',4,4',5,5'· hexachlorobiphenyl (PCB 153) decrease serum thyroxine (T4)levels in laboratory animals 1,2,3. The T4 decrease in rodents is thought to occur through the induction of UDP-glucurono...

Thyroid hormone balance in beluga whales, Delphinapterus leucas: dynamics after capture and influence of thyrotropin.

PubMed Central

St Aubin, D J; Geraci, J R

1992-01-01

Ten beluga whales, Delphinapterus leucas, were captured in the Churchill River, Manitoba, held for up to five days, and then released. Blood samples were obtained immediately after capture and at 6-7 h intervals thereafter to monitor changes in circulating levels of thyroid hormones (TH). In six of the whales, total and free thyroxine (T4) and triiodothyronine (T3) declined steadily, whereas reverse-T3 (rT3) showed a transient increase during the first 24-36 h, followed by a decrease to below initial values. The changes in TH may have been due to glucocorticoid-mediated reduction in endogenous thyroid stimulating hormone (TSH), and inhibition of 5'-monodeiodinase in peripheral tissue. Two whales were given 10 IU of bovine TSH immediately after capture, and again one and two days later, resulting in successive increases in all TH, which remained elevated for at least 24 h after the last injection. Thereafter, circulating levels declined as in the untreated whales. Two whales receiving a single TSH injection on the fourth day responded with an increase in plasma TH comparable to that observed following the first TSH injection in the other two animals. Average (+/- SD) circulating level of rT3 at capture was 6.3 +/- 3.1 nmol/L, which is higher than reported for any other mammal and was significantly correlated with the naturally elevated levels of T4 that occur in belugas occupying estuaries during the summer. PMID:1586888

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.

Rapid purification of tri-iodothyronine and thyroxine protein conjugates for antibody production.

PubMed

Burke, C W; Shakespear, R A

1975-04-01

Thyroxine (T-4) and tri-iodothyronine (T-3) were coupled to human serum albumin (HSA) with carbodi-imide. By adsorption chromatography on Sephadex G-25, fractions containing purified conjugate, but not reversibly-bound T-3 or T-4, were obtained, and this procedure took 5 h; considerably less than the conventional dialysis technique. Highly specific high-titre antisera were produced in rabbits and guinea-pigs by injection of these fractions in Freund's adjuvant.

Optimal bone strength and mineralization requires the type 2 iodothyronine deiodinase in osteoblasts

PubMed Central

Bassett, J. H. Duncan; Boyde, Alan; Howell, Peter G. T.; Bassett, Richard H.; Galliford, Thomas M.; Archanco, Marta; Evans, Holly; Lawson, Michelle A.; Croucher, Peter; St. Germain, Donald L.; Galton, Valerie Anne; Williams, Graham R.

2010-01-01

Hypothyroidism and thyrotoxicosis are each associated with an increased risk of fracture. Although thyroxine (T4) is the predominant circulating thyroid hormone, target cell responses are determined by local intracellular availability of the active hormone 3,5,3′-L-triiodothyronine (T3), which is generated from T4 by the type 2 deiodinase enzyme (D2). To investigate the role of locally produced T3 in bone, we characterized mice deficient in D2 (D2KO) in which the serum T3 level is normal. Bones from adult D2KO mice have reduced toughness and are brittle, displaying an increased susceptibility to fracture. This phenotype is characterized by a 50% reduction in bone formation and a generalized increase in skeletal mineralization resulting from a local deficiency of T3 in osteoblasts. These data reveal an essential role for D2 in osteoblasts in the optimization of bone strength and mineralization. PMID:20368437

Effect of melatonin supplementation on plasma vasopressin response to different conditions in rats with hyperthyroidism induced by L-thyroxine.

PubMed

Mogulkoc, Rasim; Baltaci, Abdulkerim Kasim

2010-04-09

The present study was performed to determine how basal, isotonic, hypertonic and hypovolemic conditions affect fluid-electrolyte balance and plasma arginine vasopressin (AVP) levels in rats with experimental hyperthyroidism supplemented with melatonin. The rats were divided into four groups of twenty-four subjects each kept under the following treatments during one month: (1) Controls; (2) treated with L-thyroxine; (3) treated with L-thyroxine and sham melatonin and (4) treated with L-thyroxine and melatonin. After this each group was further subdivided into subgroups that were subject to normal, isotonic, hypertonic and hypovolemic conditions. The plasma AVP, total triiodothyronine (TT(3)), total thyroxine (TT(4)) and melatonin levels were measured in plasma by means of a Phoenix Pharmaceutical RIA test kit. Hematocrit and osmolality levels were also determined. There were significant increases of total T3 and T4 levels in the L-thyroxine treated groups, p<0.001. The AVP levels were also increased in groups 2 and 3, but not so in the rats treated with melatonin (p<0.001), which also showed increased plasma melatonin levels (p<0.001). These results indicate that treatment with L-thyroxine increases stimulated and non-stimulated AVP release that are inhibited by melatonin supplementation. It was also shown that AVP response to hypertonic and hypovolemic conditions was not affected by L-thyroxine treatment and/or L-thyroxine+melatonin treatment. Copyright 2009 Elsevier B.V. All rights reserved.

Regulation of Ca(2+)-dependent protein turnover in skeletal muscle by thyroxine

NASA Technical Reports Server (NTRS)

Zeman, Richard J.; Bernstein, Paul L.; Ludemann, Robert; Etlinger, Joseph D.

1986-01-01

Dantrolene, an agent that inhibits Ca(2+) mobilization, improved protein balance in skeletal muscle, as thyroid status was increased, by altering rates of protein synthesis and degradation. Thyroxine (T4) caused increases in protein degradation that were blocked by leupeptin, a proteinase inhibitor previously shown to inhibit Ca(2+)-dependent nonlysosomal proteolysis in these muscles. In addition, T4 abolished sensitivity to the lysosomotropic agent methylamine and the autophagy inhibitor 3-methyladenine, suggesting that T4 inhibits autophagic/lysosomal proteolysis.

[Effect of extracts from Dendrobii ifficinalis flos on hyperthyroidism Yin deficiency mice].

PubMed

Lei, Shan-shan; Lv, Gui-yuan; Jin, Ze-wu; Li, Bo; Yang, Zheng-biao; Chen, Su-hong

2015-05-01

Some unhealthy life habits, such as long-term smoking, heavy drinking, sexual overstrain and frequent stay-up could induce the Yin deficiency symptoms of zygomatic red and dysphoria. Stems of Dendrobii officinalis flos (DOF) showed the efficacy of nourishing Yin. In this study, the hyperthyroidism Yin deficiency model was set up to study the yin nourishing effect and action mechanism of DOF, in order to provide the pharmacological basis for developing DOF resources and decreasing resource wastes. ICR mice were divided into five groups: the normal control group, the model control group, the positive control group and DOF extract groups (6.4 g · kg(-1)). Except for the normal group, the other groups were administrated with thyroxine for 30 d to set up the hyperthyroidism yin deficiency model. At the same time, the other groups were administrated with the corresponding drugs for 30 d. After administration for 4 weeks, the signs (facial temperature, pain domain, heart rate and autonomic activity) in mice were measured, and the facial and ear micro-circulation blood flow were detected by laser Doppler technology. After the last administration, all mice were fasted for 12 hours, blood were collected from their orbits, and serum were separated to detect AST, ALT, TG and TP by the automatic biochemistry analyzer and test T3, T4 and TSH levels by ELISA. (1) Compared with the normal control group, the model control group showed significant increases in facial and ear micro-circulation blood flow, facial temperature and heart rate (P < 0.05, P < 0.01), serum AST, ALT (P < 0.01), T3 level (P < 0.05), TSH level (P < 0.05) and notable deceases in pain domain (P < 0.01), TG level (P < 0.01). (2) Compared with the model control group, extracts from DOF (6 g · kg(-1)) could notably reduce facial and ear micro-circulation blood flow, facial temperature and heart rate (P < 0.05, P < 0.01) and AST (P < 0.05) and enhance pain domain (P < 0.01) and TG (P < 0.01). Extracts from DOF (4 g · kg(-1)) could remarkably reduce AST and ALT levels (P < 0.01, 0.05). Extracts from DOF (6 g · kg(-1) 4 g · kg(-1)) could significantly reduce T3 and increase serum TSH level (P < 0.05). DOF could improve Yin deficiency symptoms of zygomatic red and dysphoria in mice as well as liver function injury caused by overactive thyroid axis. According to its action mechanism, DOF may show yin nourishing and hepatic protective effects by impacting thyroxin substance metabolism, improving micro-circulation and reducing heart rate.

Congenital hypothyroidism: influence of disease severity and L-thyroxine treatment on intellectual, motor, and school-associated outcomes in young adults.

PubMed

Oerbeck, Beate; Sundet, Kjetil; Kase, Bengt F; Heyerdahl, Sonja

2003-10-01

To describe intellectual, motor, and school-associated outcome in young adults with early treated congenital hypothyroidism (CH) and to study the association between long-term outcome and CH variables acting at different points in time during early development (CH severity and early L-thyroxine treatment levels [0-6 years]). Neuropsychological tests were administered to all 49 subjects with CH identified during the first 3 years of the Norwegian neonatal screening program (1979-1981) at a mean age of 20 years and to 41 sibling control subjects (mean age: 21 years). The CH group attained significantly lower scores than control subjects on intellectual, motor, and school-associated tests (total IQ: 102.4 [standard deviation: 13] vs 111.4 [standard deviation: 13]). Twelve (24%) of the 49 CH subjects had not completed senior high school, in contrast to 6% of the control subjects. CH severity (pretreatment serum thyroxine [T4]) correlated primarily with motor tests, whereas early L-thyroxine treatment levels were related to verbal IQ and school-associated tests. In multiple regression analysis, initial L-thyroxine dose (beta = 0.32) and mean serum T4 level during the second year (beta = 0.48) predicted Verbal IQ, whereas mean serum T4 level during the second year (beta = 0.44) predicted Arithmetic. Long-term outcome revealed enduring cognitive and motor deficits in young adults with CH relative to control subjects. Verbal functions and Arithmetic were associated with L-thyroxine treatment variables, suggesting that more optimal treatment might be possible. Motor outcome was associated with CH severity, indicating a prenatal effect.

Comparative effectiveness of carvedilol and propranolol on glycemic control and insulin resistance associated with L-thyroxin-induced hyperthyroidism--an experimental study.

PubMed

Bhatt, Parloop; Makwana, Dharmesh; Santani, Devdas; Goyal, Ramesh

2007-05-01

The present study was undertaken to investigate the effectiveness of adrenergic antagonists carvedilol and propranolol on L-thyroxin-induced cardiovascular and metabolic disturbances in rats. Treatment with L-thyroxin sodium (75 mg/kg body mass, s.c., every alternate day for 3 weeks), produced a significant increase in food and water intake, body temperature, heart rate, systolic blood pressure, along with an increase in serum T3, T4, and triglyceride levels. Besides a significant reduction in body mass, serum levels of TSH and cholesterol were also reduced following L-thyroxin treatment. Carvedilol (10 mg/kg body mass, orally) and propranolol (10 mg/kg body mass, i.p.) administered daily in the third week to 2 separate groups of L-thyroxin-treated animals reversed thyroxin-induced loss in body mass and rise in body temperature, blood pressure, and heart rate. Propranolol treatment increased TSH levels and decreased T3 and T4 levels in hyperthyroid animals, whereas carvedilol did not produce any effect on thyroid hormones. Carvedilol treatment reversed thyroxin induced hypertriglyceridemia, whereas propranolol treatment had no effect. Both carvedilol and propranolol prevented decrease in cholesterol levels induced by thyroxine. Compared with normal animals, L-thyroxin-treated animals showed a state of hyperglycemia, hyperinsulinaemia, impaired glucose tolerance, and insulin resistance, as inferred from elevated fasting serum glucose and insulin levels, higher area under the curve over 120 min for glucose, and decreased insulin sensitivity index (KITT). Propranolol and carvedilol treatment significantly decreased fasting serum glucose levels. Treatment with propranolol did not alter serum insulin levels, area-under-the-curve glucose, or KITT values. However, treatment with carvedilol significantly reduced area-under-the-curve glucose, decreased fasting serum insulin levels and significantly increased KITT values. In conclusion, carvedilol appears to produce favorable effects on insulin sensitivity and glycemic control and can therefore be considered as more efficacious adjunctive treatment than propranolol in hyperthyroidism.

Thyroid function and insulin sensitivity before and after bilio-pancreatic diversion.

PubMed

Gniuli, Donatella; Leccesi, Laura; Guidone, Caterina; Iaconelli, Amerigo; Chiellini, Chiara; Manto, Andrea; Castagneto, Marco; Ghirlanda, Giovanni; Mingrone, Geltrude

2010-01-01

Bilio-pancreatic diversion (BPD) induces permanent weight loss in previously severe obese patients through a malabsorptive mechanism. The aim of the study was to evaluate the modifications of circulating thyroid hormones after BPD, a surgical procedure which interferes with the entero-hepatic circulation of biliary metabolites. Forty-five patients were studied before and 2 years after BPD. Thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), anti-thyroid antibodies, iodine urinary excretion, lipid profile, insulin and glucose plasma levels were assessed. The insulin-resistance HOMA IR index was calculated, and colour Doppler ultrasonography of the neck was performed. The subjects (23%) had subclinical hypothyroidism prior to BPD (TSH levels above the normal range with normal fT3 and fT4 levels). After 2 years 40.42% of the population showed subclinical hypothyroidism, while 6.3% became frankly hypothyroid, all of them with no evidence of auto-immune thyroiditis. Most of the patients, who became sub-clinically hypothyroid only following BPD, had already thyroid alterations at the sonogram (multi-nodular euthyroid goiter and thyroidal cysts) prior to surgery. BPD increases the prevalence of subclinical or even frank hypothyroidism, without causing a defect in thyroid function itself, through several integrated mechanisms. (1) It induces iodine malabsorption, which is partially compensated by iodine excretion contraction. (2) The entero-hepatic open circulation determines fT3 loss, which induces subclinical or frank hypothyroidism in patients with pre-existing thyroid alterations, interfering also with the weight loss progress. Iodine supplementation should be recommended in those patients reporting thyroid alterations at the sonogram prior to BPD, LT4 therapy should be strictly monitored in patients suffering of subclinical hypopthiroidism and T3 therapy should eventually be considered for patients diagnosed with frank hypothyroidism prior to BPD.

Circulating concentrations of free thyroxine after an oral intake of liquid LT4 taken either during fasting conditions or at breakfast.

PubMed

Marina, Michela; Ceda, Gian Paolo; Aloe, Rosalia; Gnocchi, Cecilia; Ceresini, Graziano

2017-01-16

Liquid levothyroxine (LT4) given at breakfast normalizes TSH in hypothyroid patients. However, a few studies are available on circulating free thyroxine (FT4) concentrations after liquid vs solid LT4 preparations. During an "ad interim" analysis on serum FT4 after 200 mcg liquid LT4 consumption while fasting in thyroidectomized thyroid cancer patients, we found that seven subjects fortuitously took liquid LT4 at breakfast. As established in the original protocol, serum FT4 was measured both at baseline as well as at 3 and 4 hours after solid or liquid LT4 consumption. We compared serum profile of FT4 in these subjects with those obtained in other subjects participating in the same study who took liquid LT4 (n. 7 subjects) or solid LT4 (n. 7 subjects) while fasting. The percentage increase of circulating FT4 was calculated at the above reported peak-times over the baseline values. Circulating FT4 increased of about 40% in each group of subjects at both the 3rd and the 4th hour with no difference between these two time points in either group. The maximum FT4 % increase, irrespective of the time point, was 44.62 ± 3.05 (Mean ± SE), 44.84 ± 5.43, and 43.83 ± 1.30 after fasting solid, fasting liquid, and breakfast liquid LT4 consumption, respectively, with no differences among the three groups. Circulating FT4 obtained after 3 and 4 hours from the ingestion of 200 mcg liquid LT4 is not influenced by meal and is comparable with that observed after solid LT4 preparations ingested while fasting.

Thyroid hormones in the elderly sick: "T4 euthyroidism".

PubMed

Burrows, A W; Shakespear, R A; Hesch, R D; Cooper, E; Aickin, C M; Burke, C W

1975-11-22

Thyroid function and serum levels of triiodothyronine (T3) and thyroxine (T4) were investigated in 79 euthyroid geriatric patients. Of the 59 inpatients and 20 outpatients 35 (59%) and 2, respectively, had low T3 levels. In contrast, 7 (12%) and 6 (30%), respectively, had raised T4 levels. Two further patients were excluded from the study because of raised levels of thyroid-stimulating hormone. Thyroxine-binding globulin was greatly increased in both groups of patients, but low serum albumin levels were present in 31 (39%). Despite these changes free T3 and T4 indices closely followed total T3 and T4 levels. The difference between the two groups of patients did not correlate with body weight, diagnostic categories, age, drug treatment, or duration of stay in hospital.

Thyroid hormones in the elderly sick: "T4 euthyroidism".

PubMed Central

Burrows, A W; Shakespear, R A; Hesch, R D; Cooper, E; Aickin, C M; Burke, C W

1975-01-01

Thyroid function and serum levels of triiodothyronine (T3) and thyroxine (T4) were investigated in 79 euthyroid geriatric patients. Of the 59 inpatients and 20 outpatients 35 (59%) and 2, respectively, had low T3 levels. In contrast, 7 (12%) and 6 (30%), respectively, had raised T4 levels. Two further patients were excluded from the study because of raised levels of thyroid-stimulating hormone. Thyroxine-binding globulin was greatly increased in both groups of patients, but low serum albumin levels were present in 31 (39%). Despite these changes free T3 and T4 indices closely followed total T3 and T4 levels. The difference between the two groups of patients did not correlate with body weight, diagnostic categories, age, drug treatment, or duration of stay in hospital. PMID:811313

Treatment and therapeutic monitoring of canine hypothyroidism.

PubMed

Dixon, R M; Reid, S W J; Mooney, C T

2002-08-01

Thirty-one dogs with spontaneous hypothyroidism were treated with thyroid hormone replacement therapy (THRT) and monitored for approximately three months. Good clinical and laboratory control was ultimately achieved in all cases with a mean L-thyroxine (T4) dose of 0.026 mg/kg administered once daily. There was a significant increase and decrease in circulating total T4 and canine thyroid stimulating hormone (cTSH) concentrations, respectively, after starting THRT. After commencing treatment, 11 cases subsequently required an increase and three cases required a decrease in dose to achieve optimal clinical control. Median (semi interquartile range [SIR]) circulating six-hour post-pill total T4 (53.6 [27.91 nmol/litre) and cTSH (0.03 [0] microg/litre) concentrations were significantly increased and decreased, respectively, in treated dogs that did not require a dose change; corresponding values in treated dogs in which an increase in dose was required were 29.3 (12.7) nmol/litre and 0.15 (0.62) microg/litre, respectively. However, circulating cTSH measurement was of limited value in assessing therapeutic control because, although increased values were associated with inadequate therapy, reference range cTSH values were common in inadequately treated dogs. Lethargy and mental demeanour were typically the first clinical signs to improve, with significant bodyweight reduction occurring within two weeks of commencing THRT. Routine clinicopathological monitoring was of value in confirming a general metabolic response to THRT, but was of limited value in accurately monitoring cases or tailoring therapy in individual cases.

The relationship between thyroxine, oestradiol, and postnatal alopecia, with relevance to women's health in general.

PubMed

Pringle, T

2000-11-01

Post-partum hair loss is possibly due to a reduction in the levels of oestradiol and thyroxine postnatally. Alopecia and/or a persistent loss of hair condition postnatally is associated with a group of symptoms (a syndrome), wherein postnatal depression is significant, as a result of physiologically inadequate levels of thyroxine (T4) and oestradiol (E2), secondary to physiological postnatal anterior pituitary dysfunction. Using this hypothesis, the author began to apply the same hypothesis to other female patients, who were not postpartum, but with similar symptomatology. The author became aware of the necessity for an adequate level of T4 to be present for correct oestrogenization to occur. He then goes on to hypothesize on the synergistic relationship that T4 and oestradiol may have in premenstrual syndrome (PMS), infertility, dysfunctional uterine bleeding, poor placental function, osteoporosis, and anorexia nervosa. He also discusses the role lowering T4 could play in the treatment of terminal cancer breast in premenopausal women.

Triclosan Disrupts Thyroxine: Contribution of Hepatic Transport to the Mode of Action

EPA Science Inventory

Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) (TCS) decreases serum thyroxine (T4) in rats. In previous work, TCS upregulated Phase I and II hepatic metabolism after 4-day exposures in rats. A major data gap in our characterization of the mode of action (MOA) of TCS-induced ...

Thyroxine (T4) Transfer from Blood to Cerebrospinal Fluid in Sheep Isolated Perfused Choroid Plexus: Role of Multidrug Resistance-Associated Proteins and Organic Anion Transporting Polypeptides

PubMed Central

Zibara, Kazem; Zein, Nabil El; Sabra, Mirna; Hneino, Mohammad; Harati, Hayat; Mohamed, Wael; Kobeissy, Firas H.; Kassem, Nouhad

2017-01-01

Thyroxine (T4) enters the brain either directly across the blood–brain barrier (BBB) or indirectly via the choroid plexus (CP), which forms the blood–cerebrospinal fluid barrier (B-CSF-B). In this study, using isolated perfused CP of the sheep by single-circulation paired tracer and steady-state techniques, T4 transport mechanisms from blood into lateral ventricle CP has been characterized as the first step in the transfer across the B-CSF-B. After removal of sheep brain, the CPs were perfused with 125I-T4 and 14C-mannitol. Unlabeled T4 was applied during single tracer technique to assess the mode of maximum uptake (Umax) and the net uptake (Unet) on the blood side of the CP. On the other hand, in order to characterize T4 protein transporters, steady-state extraction of 125I-T4 was measured in presence of different inhibitors such as probenecid, verapamil, BCH, or indomethacin. Increasing the concentration of unlabeled-T4 resulted in a significant reduction in Umax%, which was reflected by a complete inhibition of T4 uptake into CP. In fact, the obtained Unet% decreased as the concentration of unlabeled-T4 increased. The addition of probenecid caused a significant inhibition of T4 transport, in comparison to control, reflecting the presence of a carrier mediated process at the basolateral side of the CP and the involvement of multidrug resistance-associated proteins (MRPs: MRP1 and MRP4) and organic anion transporting polypeptides (Oatp1, Oatp2, and Oatp14). Moreover, verapamil, the P-glycoprotein (P-gp) substrate, resulted in ~34% decrease in the net extraction of T4, indicating that MDR1 contributes to T4 entry into CSF. Finally, inhibition in the net extraction of T4 caused by BCH or indomethacin suggests, respectively, a role for amino acid “L” system and MRP1/Oatp1 in mediating T4 transfer. The presence of a carrier-mediated transport mechanism for cellular uptake on the basolateral membrane of the CP, mainly P-gp and Oatp2, would account for the efficient T4 transport from blood to CSF. The current study highlights a carrier-mediated transport mechanism for T4 movement from blood to brain at the basolateral side of B-CSF-B/CP, as an alternative route to BBB. PMID:28588548

Pyrroloquinoline quinone ameliorates l-thyroxine-induced hyperthyroidism and associated problems in rats.

PubMed

Kumar, Narendra; Kar, Anand; Panda, Sunanda

2014-08-01

Pyrroloquinoline quinone (PQQ) is believed to be a strong antioxidant. In this study, we have evaluated its hitherto unknown role in l-thyroxin (L-T4 )-induced hyperthyroidism considering laboratory rat as a model. Alterations in the serum concentration of thyroxin (T4 ) and triiodothyronine (T3 ); lipid peroxidation (LPO) of liver, kidney, heart, muscles and brain; in the endogenous antioxidants such as superoxide dismutase, catalase and glutathione and in serum total cholesterol, high-density lipoprotien, triglycerides, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and urea were evaluated. Administration of l-T4 (500-µg kg(-1) body weight) enhanced not only the serum T3 and T4 levels but also the tissue LPO, serum SGOT, SGPT and urea with a parallel decrease in the levels of antioxidants and serum lipids. However, on simultaneous administration of PQQ (5 mg kg(-1) for 6 days), all these adverse effects were ameliorated, indicating the potential of PQQ in the amelioration of hyperthyroidism and associated problems. Possibly, the curative effects were mediated through inhibition of oxidative stress. We suggest that PQQ may be considered for therapeutic use for hyperthyroidism after dose standardization. Copyright © 2014 John Wiley & Sons, Ltd.

Developmental Triclosan Exposure Decreases Maternal and Offspring Thyroxine in Rats*

EPA Science Inventory

Epidemiological and laboratory data have demonstrated that disruption of maternal thyroid hormones during fetal developmental may result in irreversible neurological consequences in offspring. In a short-term exposure paradigm, triclosan decreased systemic thyroxine (T4) concentr...

Serum thyroxine concentrations after radioactive iodine therapy in cats with hyperthyroidism

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

Meric, S.M.; Hawkins, E.C.; Washabau, R.J.

Thirty-one cats with hyperthyroidism were given one dose of radioactive iodine (131I) IV. Serum thyroxine (T4) concentrations were measured before treatment in all cats, at 12-hour intervals after treatment in 10 cats, and at 48-hour intervals after treatment in 21 cats. Serum T4 concentrations also were measured one month after /sup 131/I therapy in 29 cats. Activity of 131I administered was 1.5 to 6.13 mCi, resulting in a dose of 20,000 rads to the thyroid. Serum T4 concentrations before /sup 131/I administration were 5.3 to 51.0 micrograms/dl, with a median T4 concentration of 11.0 micrograms/dl. Serum T4 decreased most rapidlymore » during the first 3 to 6 days after treatment. Sixteen cats (55%) had normal serum thyroxine concentrations by day 4 after 131I administration, and 23 cats (74%) were euthyroxinemic by day 8 after treatment. One month after administration of 131I, the 29 cats evaluated were clinically improved, and 24 (83%) of the 29 cats evaluated had normal serum T4 concentrations, 3 cats (10%) remained hyperthyroxinemic, and 2 cats (7%) were hypothyroxinemic. Therefore, administration of 131I was a safe and effective method to quickly decrease serum T4 concentrations in hyperthyroid cats.« less

Triiodothyronine and thyroxine in urine. I. Measurement and application.

PubMed

Shakespear, R A; Burke, C W

1976-03-01

Urinary triiodothyronine (T3) and thyroxine (T4) were measured by RIA, and T4 was also measured by competitive protein binding (CPB). pH 1-hydrolysable conjugates were 48% of total urinary T3, and enzyme- or pH 1-hydrolysable conjugates were 55% and 61% of total urinary T4. The mean unconjugated T3 excretion was 34.3 ng/h (0.99 mug T3/g creatinine) in normal subjects (no day-night rhythm found), 1.56 mug/g in late pregnancy, 0.82 mug/g in neonates (1-12 days), and was also unchanged in persons with high or low thyroxine-binding globulin (TBG). In thyrotoxicosis, mean T3 excretion was 281 ng/h, no values being in the normal range. In primary hypothyroidism it was 18.3 ng/h, but over half the values were in the normal range. The mean urinary unconjugated T4 was 82.2 ng/h (1.37 mug T4/g creatinine) in normal subjects, 1.6 mug/g in neonates, and unchanged in persons with high or low TBG, except that in pregnancy high values were compatible with increases protein excretion. Apparently increased day-time T4 excretion compared with night-time excretion may also be due to changes in protein excretion rate. The mean T4 in thyrotoxicosis was 337 ng/h (12% of values in the normal range) and 32.8 ng/h in primary hypothyroidism (over half the normal range). All the assays, especially that of T4 by CPB gave readings which were incorrect with protein concentrations above 100 mg/l. Urinary T3 and T4 assays for clinical purposes have few practical advantages over serum assays, despite the relationship of urine T3 and T4 to serum unbound levels.

Distinct Genetic Signatures for Variability in Total and Free Serum Thyroxine Levels in Four Sets of Recombinant Inbred Mice

PubMed Central

Lu, Lu; Aliesky, Holly A.; Williams, Robert W.; Rapoport, Basil

2011-01-01

C3H/He and BALB/c mice have elevated serum thyroxine levels associated with low deiodinase type-1 activity whereas C57BL/6 (B6) mice have low thyroxine levels and elevated deiodinase type-1 activity. High-resolution genetic maps are available for four sets of recombinant inbred (RI) mice derived from B6 parents bred to C3H/He, BALB/c, DBA/2, or A strains. Total and free T4 (T-T4 and F-T4) levels in females from these RI sets (BXH, CXB, BXD, and AXBXA) were analyzed to test two hypotheses: first, serum T4 variability is linked to the deiodinase type-1 gene; second, because of their shared B6 parent, the RI sets will share linkages responsible for T-T4 or F-T4 variability. A number of chromosomes (Chr) and loci were linked to T-T4 (Chr 1, 4, 13, 11) or F-T4 (Chr 1, 6, 13, 18, 19). Linkage between T-T4 and Chr 4 was limited to CXB and BXH strains, but the locus was distinct from the deiodinase type-1 gene. Surprisingly, many linkages were unique providing “genetic signatures” for T-T4 or F-T4 in each set of RI mice. Indeed, the strongest linkage between T-T4 (or F-T4) and a Chr 2 locus (logarithm of the odds scores >4.4) was only observed in AXBXA strains. Some loci corresponded to genes/Chr associated in humans with variable TSH or T-T4 levels. Unlike inbred mice, human populations are extremely diverse. Consequently, our data suggest that the contributions of unique chromosomes/loci controlling T-T4 and F-T4 in distinct human subgroups are likely to be “buried” in genetic analyses of heterogeneous human populations. PMID:21209025

Thyroxin treatment protects against white matter injury in the immature brain via brain-derived neurotrophic factor.

PubMed

Hung, Pi-Lien; Huang, Chao-Ching; Huang, Hsiu-Mei; Tu, Dom-Gene; Chang, Ying-Chao

2013-08-01

Low level of thyroid hormone is a strong independent risk factor for white matter (WM) injury, a major cause of cerebral palsy, in preterm infants. Thyroxin upregulates brain-derived neurotrophic factor during development. We hypothesized that thyroxin protected against preoligodendrocyte apoptosis and WM injury in the immature brain via upregulation of brain-derived neurotrophic factor. Postpartum (P) day-7 male rat pups were exposed to hypoxic ischemia (HI) and intraperitoneally injected with thyroxin (T4; 0.2 mg/kg or 1 mg/kg) or normal saline immediately after HI at P9 and P11. WM damage was analyzed for myelin formation, axonal injury, astrogliosis, and preoligodendrocyte apoptosis. Neurotrophic factor expression was assessed by real-time polymerase chain reaction and immunohistochemistry. Neuromotor functions were measured using open-field locomotion (P11 and P21), inclined plane climbing (P11), and beam walking (P21). Intracerebroventricular injection of TrkB-Fc or systemic administration of 7,8-dihydroxyflavone was performed. On P11, the HI group had significantly lower blood T4 levels than the controls. The HI group showed ventriculomegaly and marked reduction of myelin basic protein immunoreactivities in the WM. T4 (1 mg/kg) treatment after HI markedly attenuated axonal injury, astrocytosis, and microgliosis, and increased preoligodendrocyte survival. In addition, T4 treatment significantly increased myelination and selectively upregulated brain-derived neurotrophic factor expression in the WM, and improved neuromotor deficits after HI. The protective effect of T4 on WM myelination and neuromotor performance after HI was significantly attenuated by TrkB-Fc. Systemic 7,8-dihydroxyflavone treatment ameliorated hypomyelination after HI injury. T4 protects against WM injury at both pathological and functional levels via upregulation of brain-derived neurotrophic factor-TrkB signaling in the immature brain.

Effect of propranolol on thyroid homeostasis of healthy volunteers.

PubMed Central

Wilkins, M. R.; Franklyn, J. A.; Woods, K. L.; Kendall, M. J.

1985-01-01

The effect of propranolol on thyroid status was investigated by administering the drug in 2 therapeutic doses (80 mg b.d. and 120 mg b.d.) to 8 healthy volunteers and serially measuring total and free thyroid hormones and their major binding protein. Mean free T3 fell by 1.2 pmol/l (P less than 0.05) whilst mean free T4 and mean rT3 rose by 3.3 pmol/l (P less than 0.01) and 0.16 nmol/l (P less than 0.01) respectively. Mean thyroxine binding globulin (TBG) fell by 1.2 mg/l (P less than 0.001). Despite the change in free hormone levels there was no significant change in TSH. For the first time the effect of propranolol on circulating thyroid hormones and binding proteins in healthy subjects is apparent within one study. The biological significance of the change in free hormone levels is discussed. PMID:3927277

The History and Future of Treatment of Hypothyroidism

PubMed Central

McAninch, Elizabeth A.; Bianco, Antonio C.

2016-01-01

Thyroid hormone replacement has been used for more than a century to treat hypothyroidism. Natural thyroid preparations (thyroid extract, desiccated thyroid, or thyroglobulin), which contain both thyroxine (T4) and triiodothyronine (T3), were the first pharmacologic treatments available and dominated the market for the better part of the 20th century. Dosages were adjusted to resolve symptoms and to normalize the basal metabolic rate and/or serum protein-bound iodine level, but thyrotoxic adverse effects were not uncommon. Two major developments in the 1970s led to a transition in clinical practice: 1) The development of the serum thyroid-stimulating hormone (TSH) radioimmunoassay led to the discovery that many patients were overtreated, resulting in a dramatic reduction in thyroid hormone replacement dosage, and 2) the identification of peripheral deiodinase-mediated T4-to-T3 conversion provided a physiologic means to justify l-thyroxine monotherapy, obviating concerns about inconsistencies with desiccated thyroid. Thereafter, l-thyroxine mono-therapy at doses to normalize the serum TSH became the standard of care. Since then, a subgroup of thyroid hormone–treated patients with residual symptoms of hypothyroidism despite normalization of the serum TSH has been identified. This has brought into question the inability of l-thyroxine monotherapy to universally normalize serum T3 levels. New research suggests mechanisms for the inadequacies of l-thyroxine monotherapy and highlights the possible role for personalized medicine based on deiodinase polymorphisms. Understanding the historical events that affected clinical practice trends provides invaluable insight into formulation of an approach to help all patients achieve clinical and biochemical euthyroidism. PMID:26747302

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

Measurement of thyroxine and its glucuronide in municipal wastewater and solids using weak anion exchange solid phase extraction and ultrahigh performance liquid chromatography-tandem mass spectrometry.

PubMed

Brown, Alistair K; Wong, Charles S

2017-11-24

A solids extraction method, using sonication in combination with weak anion exchange solid phase extraction, was created to extract thyroxine (T4) and thyroxine-O-β-d-glucuronide (T4-Glc) simultaneously from wastewaters and sludges, and to quantify these compounds via reversed-phase ultra-high performance liquid chromatography-tandem mass spectrometry. The method limits of quantification were all in the low ng/g (dry weight solids) range for both T4 and T4-Glc: 2.13 and 2.63ng/g respectively in primary wastewater, 4.3 and 28.3ng/g for primary suspended solids, for 1.1 and 3.7ng/g for return activated sludge. Precision for measurements of T4 and T4-Glc were 2.6 and 6.5% (intraday) and 9.6 and 5.7% (interday) respectively, while linearity was 0.9967 and 0.9943 respectively. Overall recoveries for T4 and T4-Glc in primary suspended solids were 94% and 95%, and 86 and 101% in primary wastewater, respectively. Extraction efficiency tests using primary sludge determined that one methanol aliquot was sufficient during the extraction process as opposed to 2 or 3 aliquots. Mass loadings at the North Main Wastewater Treatment Plant in Winnipeg, Canada showed 316%, 714%, and 714% greater T4-Glc than T4 associated with the suspended solids of the primary, secondary, and final effluent respectively, yet 765% more T4 than T4-Glc associated with the solids of the mixed liquor. Moreover, 26% of T4 and 49% of T4-Glc were associated with the suspended solids during the treatment process. This method demonstrates the need to assess accurately both metabolite conjugates of contaminants of emerging concern, as well as the sorbed levels of particle-reactive analytes such as T4 in the aquatic environment. Copyright © 2017 Elsevier B.V. All rights reserved.

Radioimmunoassay of ''free thyroxin'' in dried blood spots on filter paper - preliminary observations on the effective differentiation of subjects with congenital hypothyroidism from those with subnormal thyroxin-binding globulin and normal subjects

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

Mizuta, H.; Miyai, K.; Ichihara, K.

1982-03-01

In this sensitive, simple method for measuring ''free thyroxin'' (FT/sub 4/) in eluates of dried blood spots on filter paper by use of a radioimmunoassay kit (Amerlex Free T/sub 4/ RIA), the measurable range of FT/sub 4/ is 1.8 to 57 ng/L (equivalent to the concentration in serum), or 7 to 237 fg/tube. The mean coefficients of variation for within assay-within spots, within assay-between spots, and between assays were 5.3%, 5.0%, and 6.2%, respectively. FT/sub 4/ in blood spotted on filter paper is stable for at least a month when dried and kept at either -20/sup 0/C, 4/sup 0/C, roommore » temperature (about 25/sup 0/C), or 37/sup 0/C. The results for FT/sub 4/ in dried blood spots correlated closely with the free-T/sub 4/ concentration in serum (r = 0.99). The method can be used to differentiate cases of primary and secondary hypothyroidism from normal subjects and those with subnormal thyroxin-binding globulin. This method may be useful in screening for congenital hypothyroidism, because sample-retesting is not necessary.« less

Effects of melatonin on lipid peroxidation and anti-oxidant enzyme activity in rats with experimentally induced hyperthyroidism.

PubMed

Baydas, Burhanettin; Meral, Ismail

2005-07-01

1. The present study was designed to investigate the effects of high-dose melatonin on lipid peroxidation and anti-oxidant enzyme activity in rats with experimentally induced hyperthyroidism. 2. Twenty-four albino male rats, weighing 240-260 g, were randomly allotted into one of three experimental groups (control, hyperthyroid and hyperthyroid + melatonin treatment), with each group containing eight animals. Hyperthyroidism was induced by a daily with i.p. injection of 200 microg l-thyroxine for 30 days. In addition to l-thyroxin treatment, rats in the hyperthyroid + melatonin treatment group were also given daily i.p. injections of 10 mg/kg melatonin on the last 10 days of l-thyroxine treatment. Control animals received injections of an equivalent volume of saline solution. Rats received the last injection 24 h before being killed. 3. At the end of the experiment, rats in all three groups were fasted for 12 h and killed by cardiac puncture under ether anaesthesia. Blood samples were taken for the determination of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) levels and concentrations of tri-iodothyronine (T(3)) and thyroxine (T(4)). 4. It was found that MDA and SOD levels and concentrations of T(3) and T(4) were higher and the GSH level was lower in rats with hyperthyroidism compared with controls. Melatonin treatment decreased the elevated MDA and SOD levels and increased the lowered GSH level to control levels in rats with hyperthyroidism, but did not ameliorate the concentrations of T(3) and T(4). 5. It was concluded that high-dose melatonin treatment may decrease the hyperthyroidism-induced disturbances of lipid peroxidation and anti-oxidant enzyme activity and oxidative damage.

Developmental triclosan exposure decreases maternal, fetal, and early neonatal thyroxine: a dynamic and kinetic evaluation of a putative mode-of-action.

PubMed

Paul, Katie B; Hedge, Joan M; Bansal, Ruby; Zoeller, R Thomas; Peter, Robert; DeVito, Michael J; Crofton, Kevin M

2012-10-09

This work tests the mode-of-action (MOA) hypothesis that maternal and developmental triclosan (TCS) exposure decreases circulating thyroxine (T4) concentrations via up-regulation of hepatic catabolism and elimination of T4. Time-pregnant Long-Evans rats received TCS po (0-300mg/kg/day) from gestational day (GD) 6 through postnatal day (PND) 21. Serum and liver were collected from dams (GD20, PND22) and offspring (GD20, PND4, PND14, PND21). Serum T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations were measured by radioimmunoassay. Ethoxy-O-deethylase (EROD), pentoxyresorufin-O-depentylase (PROD) and uridine diphosphate glucuronyltransferase (UGT) enzyme activities were measured in liver microsomes. Custom Taqman(®) qPCR arrays were employed to measure hepatic mRNA expression of select cytochrome P450s, UGTs, sulfotransferases, transporters, and thyroid hormone-responsive genes. TCS was quantified by LC/MS/MS in serum and liver. Serum T4 decreased approximately 30% in GD20 dams and fetuses, PND4 pups and PND22 dams (300mg/kg/day). Hepatic PROD activity increased 2-3 fold in PND4 pups and PND22 dams, and UGT activity was 1.5 fold higher in PND22 dams only (300mg/kg/day). Minor up-regulation of Cyp2b and Cyp3a expression in dams was consistent with hypothesized activation of the constitutive androstane and/or pregnane X receptor. T4 reductions of 30% for dams and GD20 and PND4 offspring with concomitant increases in PROD (PND4 neonates and PND22 dams) and UGT activity (PND22 dams) suggest that up-regulated hepatic catabolism may contribute to TCS-induced hypothyroxinemia during development. Serum and liver TCS concentrations demonstrated greater fetal than postnatal internal exposure, consistent with the lack of T4 changes in PND14 and PND21 offspring. These data support the MOA hypothesis that TCS exposure leads to hypothyroxinemia via increased hepatic catabolism; however, the minor effects on thyroid hormone metabolism may reflect the low efficacy of TCS as thyroid hormone disruptor or highlight the possibility that other MOAs may also contribute to the observed maternal and early neonatal hypothyroxinemia. Published by Elsevier Ireland Ltd.

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.

Effect of thyroxine supplementation on glomerular filtration rate in hypothyroid dogs.

PubMed

Gommeren, K; van Hoek, I; Lefebvre, H P; Benchekroun, G; Smets, P; Daminet, S

2009-01-01

Glomerular filtration rate (GFR) is decreased in humans with hypothyroidism, but information about kidney function in dogs with hypothyroidism is lacking. Hypothyroidism influences GFR in dogs. The objective of this study was to assess GFR in hypothyroid dogs before implementation of thyroxine supplementation and after re-establishing euthyroidism. Fourteen hypothyroid dogs without abnormalities on renal ultrasound examination or urinalysis. Blood pressure and GFR (measured by exogenous creatinine clearance) were measured before treatment (T0, n=14) and at 1 month (T1, n=14) and at 6 months (T6, n=11) after beginning levothyroxine supplementation therapy (20 microg/kg/d, PO). The response to therapy was monitored at T1 by measuring serum total thyroxine and thyroid stimulating hormone concentrations. If needed, levothyroxine dosage was adjusted and reassessed after 1 month. Statistical analysis was performed using a general linear model. Results are expressed as mean+/-standard deviation. At T0, the average age of dogs in the study group was 6.3+/-1.4 years. Their average body weight decreased from 35+/-18 kg at T0 to 27+/-14 kg at T6 (P<.05). All dogs remained normotensive throughout the study. GFR increased significantly with levothyroxine supplementation; the corresponding results were 1.6+/-0.4 mL/min/kg at T0, 2.1+/-0.4 at T1, and 2.0+/-0.4 at T6 (P<.01). GFR was <2 mL/min/kg in untreated hypothyroid dogs. Re-establishment of a euthyroid state increased GFR significantly.

Anticonvulsants and thyroid function.

PubMed Central

Yeo, P P; Bates, D; Howe, J G; Ratcliffe, W A; Schardt, C W; Heath, A; Evered, D C

1978-01-01

Serum total and free thyroid hormone concentrations were estimated in 42 patients with epilepsy taking anticonvulsants (phenytoin, phenobarbitone, and carbamazepine either singly or in combination). There was a significant reduction in total thyroxine (TT4), free thyroxine (FT4), and free triiodothyronine (FT3) in the treated group compared with controls. Free hormone concentrations were lower than total hormone concentrations, suggesting that increased clearance of thyroid hormones occurs in patients receiving anticonvulsants. Detailed analysis indicated that phenytoin had a significant depressant effect on TT4, FT4, FT3, and reverse T3 (rT3). Phenobarbitone and carbamazepine had no significant main effects, but there were significant interactions between phenytoin and carbamazepine for TT4 and FT4. phenobarbitone and carbamazepine for FT3, and phenytoin and phenobarbitone for rT3. PMID:656820

Pharmacokinetics of total thyroxine in dogs after administration of an oral solution of levothyroxine sodium.

PubMed

Le Traon, G; Burgaud, S; Horspool, L J I

2008-04-01

Oral L-thyroxine (L-T4) supplementation is used to replace thyroid hormone concentrations in dogs with hypothyroidism. The pharmacokinetics of L-T4 following administration of a solution (Leventa) was investigated in healthy dogs. L-T4 was absorbed fairly rapidly (t(max) 3 h). A mean bioavailability of 22% was calculated following a single oral administration of 40 microg L-T4/kg body weight. Repeated oral administration at the same dose for 14 consecutive days did not lead to any accumulation of T4 in serum. After intravenous administration of L-T4, a serum half-life of 11.6 h was calculated. Food intake concomitant with L-T4 oral administration delayed L-T4 absorption and decreased its rate and extent by about 45%. The relative bioavailability of L-T4 following administration of a tablet formulation was about 50% of that of the L-T4 solution. The pharmacokinetic properties of liquid L-T4 after oral administration support the use of a dose rate of 20 microg/kg once daily, as a starting dose for replacement therapy in dogs with hypothyroidism.

Polychlorinated Biphenyl Congeners that Increase the Glucuronidation and Biliary Excretion of Thyroxine Are Distinct from the Congeners that Enhance the Serum Disappearance of Thyroxine

PubMed Central

Martin, L. A.; Wilson, D. T.; Reuhl, K. R.; Gallo, M. A.

2012-01-01

Polychlorinated biphenyl (PCB) congeners differentially reduce serum thyroxine (T4) in rats, but little is known about their ability to affect biliary excretion of T4. Thus, male Sprague-Dawley rats were orally administered Aroclor-1254, Aroclor-1242 (32 mg/kg per day), PCB-95, PCB-99, PCB-118 (16 mg/kg per day), PCB-126 (40 μg/kg per day), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (3.9 μg/kg per day), or corn oil for 7 days. Twenty-four hours after the last dose, [125I]T4 was administered intravenously, and blood, bile, and urine samples were collected for quantifying [125I]T4 and in bile [125I]T4 metabolites. Serum T4 concentrations were reduced by all treatments, but dramatic reductions occurred in response to Aroclor-1254, PCB-99 [phenobarbital (PB)-type congener], and PCB-118 (mixed-type congener). None of the treatments increased urinary excretion of [125I]T4. Aroclor-1254, PCB-118, TCDD, and PCB-126 (TCDD-type congener) increased biliary excretion of T4-glucuronide by 850, 756, 710, and 573%, respectively, corresponding to marked induction of hepatic UDP-glucuronosyltransferase (UGT) activity toward T4. PCB-95 and PCB-99 did not induce UGT activity; therefore, the increased biliary excretion of T4-glucuronide was related to the affinity of congeners for the aryl hydrocarbon receptor. The disappearance of [125I]T4 from serum was rapid (within 15-min) and was increased by Aroclor-1254, PCB-99 and PCB-118. Thus, reductions in serum T4 in response to PCBs did not always correspond with UGT activity toward T4 or with increased biliary excretion of T4-glucuronide. The rapid disappearance of [125I]T4 from the serum of rats treated with PB-like PCBs suggests that increased tissue uptake of T4 is an additional mechanism by which PCBs may reduce serum T4. PMID:22187485

Role of Thyroxine in Space-Developed Jellyfish

NASA Technical Reports Server (NTRS)

Spangenberg, Dorothy B.

1997-01-01

The Aurelia Metamorphosis Test System was previously used to determine the effects of the space environment on the development and behavior of tiny (1-2 mm) jellyfish ephyrae during the SLS-1 and IML-2 missions. Results from the SLS-1 experiment included the discovery that statolith numbers were significantly reduced in Earth-formed ephyrae flown for nine days in space as compared with ground-based controls. In addition, upon return to Earth, six times more ephyrae which had developed in space than those developed on Earth had pulsing abnormalities, indicating that either these animals did not form their neuromuscular structures normally while in space or they were unable to adapt to the Ig environment upon return to Earth. The metamorphosis process, which enables the formation of ephyrae from polyps is influenced by a hormone, Jf-T4 Oellyfish thyroxine) which is synthesized following iodine administration. Two groups of polyps in space, however, formed ephyrae without iodine administration indicating that Jf-T4 synthesis, utilization, or excretion was different in. the ephyrae. Increased synthesis or build-up in the media of the hormone may also be linked to the increased demineralization of statoliths found in space-exposed ephyrae. In previous experiments, we found that externally administered thyroxine causes increased demineralization of statoliths on Earth. Abnormal pulsina in ephyrae following return to Earth during the SLS-1 mission may also be traced to increased Jf-T4 levels. Thyroxine is known to be important to the normal development and function of the nervous system, heart, and skeletal muscles in higher animals. For this third Jellyfish-in-Space experiment, we proposed to quantitate the levels of Jf- T4 and of T4 receptors in space-developed ephyrae and media and to compare these levels with those of animals developing and at Ig in space and on Earth. We expected to be able to determine whether Jf-T4 synthesis and/or secretion is different in space-flownjellyfish than in controls and to determine which cells (nerve, muscle, lithocytes, etc.)may have enhanced Jf-T4 levels. However, NASA deselected this experiment in August, 1997.

Endothelin mechanisms in altered thyroid states in the rat.

PubMed

Rebello, S; Thompson, E B; Gulati, A

1993-06-11

Endothelin (ET) and its receptor characteristics were studied in hyper- and hypo-thyroid states in the rats. Hyperthyroidism was induced by daily administration of thyroxine (0.1 mg/kg i.p.) for 8 weeks, while hypothyrodism was induced by daily administration of methimazole (10 mg/kg i.p.) for 8 weeks. The chronic administration of thyroxine to rats decreased their rate of gain of body weight, increased serum T3 and T4 concentration, blood pressure and heart rate. The chronic administration of methimazole decreased the rate of gain of body weight, serum T3 and T4 concentration, blood pressure and heart rate as compared to vehicle-treated control. Plasma ET-1 levels were found to be similar in control and methimazole-treated rats, while the levels were found to be significantly (P < 0.002) increased in thyroxine-treated rats as compared to control rats. Binding studies showed that [125I]ET-1 bound to a single, high affinity binding site in the cerebral cortex, hypothalamus and pituitary. The density (Bmax) and the affinity (Kd) of [125I]ET-1 binding in the cerebral cortex and hypothalamus were found to be similar in control, methimazole- and thyroxine-treated rats. The pituitary of thyroxine-treated rats showed a decrease in the binding (34.3% decrease in the density) of [125I]ET-1 as compared to control rats. No difference was observed in the binding of [125I]ET-1 to pituitary membranes from control and methimazole-treated rats. Competition studies showed that the IC50 and Ki values of ET-3 for [125]ET-1 binding were about 8 to 11 times higher than ET-1 in cerebral cortex, hypothalamus and pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)

Gender disparities in screening for congenital hypothyroidism using thyroxine as a primary screen.

PubMed

DeMartino, Lenore; McMahon, Rebecca; Caggana, Michele; Tavakoli, Norma Parvin

2018-06-26

Newborn screening for congenital hypothyroidism (CH) is based on testing for the markers thyroxine (T4) and/or thyroid stimulating hormone (TSH). Diagnosis of CH is complicated because many factors affect the levels of these hormones including infant birth weight, prematurity, and age at specimen collection. We investigated whether the sex of the newborn affected the levels of T4 and TSH and consequently the outcome of newborn screening. In New York State, the Newborn Screening program initially tests all infants for T4 and any baby with a result in the lowest 10% is triaged for TSH screening. We analyzed data from 2008 to 2016 to determine mean and median T4 and TSH values and how these results correlate with the sex of infants who are reported as borderline, referred and confirmed with CH. T4 and TSH concentrations in dried blood spots were measured using commercially available fluoroimmunoassays. From 2008 to 2016, of the 2.4 million specimens tested for thyroxine, 51.5% were from male and 48.5% were from female infants. Male infants constituted 60% of specimens triaged for TSH testing, 64.9% of repeat requests and 59.6% of referrals, but only 49% of confirmed CH cases. The mean and median T4 values were lower (a difference of approximately 0.8-1.1 μg/dL each year), and the median TSH values were higher in male compared to female infants. Natural differences in thyroid hormone levels in male and female infants leads to male infants being disproportionately represented in the false positive category.

Analysis of Current Thyroid Function Testing Practices

DTIC Science & Technology

2017-10-18

electric medical record (EMR). TFTs of interest were: TSH, FT4, thyroid panel )TSH + FT4), FT3, total thyroxine (T$), and total triiodothyronine (T3). These were also categorized based on the presence or absence of hypothyroidism .

Effects of chronic treatment with 7-nitroindazole in hyperthyroid rats.

PubMed

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

2006-11-01

This study analyzed the contribution of neuronal nitric oxide synthase (nNOS) to the hemodynamic manifestations of hyperthyroidism. The effects on hyperthyroid rats of the chronic administration of 7-nitroindazole (7-NI), an inhibitor of nNOS, were studied. Six groups of male Wistar rats were used: control, 7-NI (30 mg.kg-1.day-1 by gavage), T(4)50, T(4)75 (50 or 75 microg thyroxine.rat-1.day-1, respectively), T(4)50+7-NI, and T(4)75+7-NI. All treatments were maintained for 4 wk. Body weight, tail systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, SBP, pulse pressure (PP), and HR were measured in conscious rats, and morphological, metabolic, plasma, and renal variables were determined. Expression of nNOS in the hypothalamus of T(4)75 and control rats was analyzed by Western blot analysis. The response of mean arterial pressure (MAP) to pentolinium (10 mg/kg iv) was used to evaluate the sympathetic contribution to BP in T(4)75 and T(4)75+7-NI rats. T(4) produced an increased hypothalamic nNOS expression and dose-related increases in blood pressure (BP), HR, and PP vs. control rats. 7-NI did not modify BP or any other hemodynamic variable in normal rats. However, 7-NI produced a marked reduction in BP, HR, PP, and food and water intake in both hyperthyroid groups and improved creatinine clearance in the T(4)75 group. Pentolinium produced a greater MAP decrease in the T(4)75+7-NI than in the T(4)75 group. In conclusion, administration of 7-NI attenuates the hemodynamic and metabolic manifestations of hyperthyroidism, suggesting that nNOS contributes to the hyperdynamic circulation of this endocrine disease by modulating sympathetic activity.

Analytical Application of Flow Immunosensor in Detection of Thyroxine and Triiodothyronine in Serum.

PubMed

Wani, Tanveer A; Zargar, Seema; Majid, Salma; Darwish, Ibrahim A

2016-11-01

In this study, an immunosensor based on kinetic exclusion analysis (KinExA) was used for thyroxine (T4) and triiodothyronine (T3) estimation. A KinExA™ 3200 instrument was used for this analysis, which is an automated flow fluorimeter designed to separate free unbound antibody binding sites in reaction mixtures of antibody, antigen, and antibody-antigen complex. A T3-BSA- and T4-BSA-coated polymethyl methacrylate (PMMA) bead microcolumn is generated inside the flow cell of the instrument. A sample mixture containing T3 and T4 with their respective monoclonal antibodies and their complexes are drawn past the microbead column. The unbound T3 or T4 monoclonal antibody binding sites are captured by their respective T3 and T4 antigens coated on the PMMA beads as bovine serum albumin conjugates. Fluorescently labeled secondary antibodies bind to the T3 or T4 antigen-antibody complex to generate fluorescence intensity for analysis. The limit of detection for the T3 and T4 assays was found to be 0.06 and 1.9 ng mL -1 with acceptable precision values. The convenience of the automated KinExA format may be valuable in medical diagnostic laboratories.

Triiodothyronine and thyroxine content of desiccated thyroid tablets.

PubMed

Rees-Jones, R W; Larsen, P R

1977-11-01

Triiodothyronine (T3) and thyroxine (T4) were measured by radioimmunoassay in Pronase hydrolysates of four lots each of 1- and 2-grain tablets of desiccated thyroid (Thyroid, Armour) and thyroglobulin (Proloid, Warner-Chilcott). The methodology used was verified by studies of tablets containing known quantities of T4 and T3. One grain of desiccated thyroid contained 12 +/- 1 and 64 +/- 3 microgram (mean +/- SD) of T3 and T4 per tablet, respectively (T4/T3 molar ratio, 4.3). A 1-grain tablet of thyroglobulin contained 16 +/- 2 and 55 +/- 5 microgram of T3 and T4, respectively with a T4/T3 ratio of 2.9. Two-grain tablets generally contained twice the quantity of T3 and T4 in the 1-grain preparations. The variation in T3 and T4 content between the four lots of each tablet strength for each product was 10% or less. These estimates of T3 and T4 content are 1.5- to 2-fold greater than those previously published. This difference probably results from the more sophisticated methodology now available which does not require chromatographic separation of T3 and T4 or iodometry. Using calculations based on published estimates of T4 and T3 absorption and of the T3/T4 potency ratio, it would appear that the T3 content of desiccated thyroid and thyroglobulin provide approximately 39% and 51%, respectively, of the thyromimetic activity of these two medications.

Defective Response of Natural Killer Activity to Thyroxine in Graves’ Disease

PubMed Central

Lee, Myung-Shik; Hong, Weon-Seon; Hong, Seong Woon; Lee, Jhin-Oh; Kang, Tae-Woong

1990-01-01

The effect of thyroxine (T4) on natural killer (NK) activity of peripheral blood lymphocytes (PBL) was investigated, using a 4-hr 51Cr release assay, in 18 patients with previously untreated Graves’ disease and in 18 controls. NK activity in patients with Graves disease was not significantly different from that in the controls. Normal T4 (NT) and high T4 (HT) medium, free T4 concentrations in which were 1.01 and 16.3 ng/dl, respectively, were used to evaluate the effect of T4 on NK activity. In the controls, NK activity increased in the NT or HT medium compared with that in the control medium at effector to target cell (E : T) ratios of 25 : 1 and 50 : 1. NK activity in the Graves’ disease patients, however, did not increase when either the NT or HT medium was used at E : T ratios of 25 : 1 and 50 : 1. These results suggest that patients with Graves’ disease have a similar NK activity to the controls but have a defect in the peripheral blood lymphocytes to increase NK activity in response to T4. PMID:2098098

Determining Baseline Stress-Related Hormone Values in Large Cetaceans

DTIC Science & Technology

2014-09-30

reconstructed chemical profiles provided a unique window into stress-related hormone (cortisol, aldosterone , T3 and T4) concentrations and...Stress-related hormone radioimmunoassay technique Cortisol, aldosterone , hormones thyroxine (T4) and triiodothyronine (T3) levels in each identified...contaminant concentrations will be calculated using Pearson correlation coefficients. These measurements will include all hormones ( aldosterone , T3

Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment.

PubMed

Hoermann, Rudolf; Midgley, John E M; Giacobino, Adrienne; Eckl, Walter A; Wahl, Hans Günther; Dietrich, Johannes W; Larisch, Rolf

2014-12-01

We examined the interrelationships of pituitary thyrotropin (TSH) with circulating thyroid hormones to determine whether they were expressed either invariably or conditionally and distinctively related to influences such as levothyroxine (L-T4) treatment. This prospective study employing 1912 consecutive patients analyses the interacting equilibria of TSH and free triiodothyronine (FT3) and free thyroxine (FT4) in the circulation. The complex interrelations between FT3, FT4 and TSH were modulated by age, body mass, thyroid volume, antibody status and L-T4 treatment. By group comparison and confirmation by more individual TSH-related regression, FT3 levels were significantly lower in L-T4-treated vs untreated nonhypothyroid autoimmune thyroiditis (median 4·6 vs 4·9 pm, P < 0·001), despite lower TSH (1·49 vs 2·93 mU/l, P < 0·001) and higher FT4 levels (16·8 vs 13·8 pm, P < 0·001) in the treated group. Compared with disease-free controls, the FT3-TSH relationship was significantly displaced in treated patients with carcinoma, with median TSH of 0·21 vs 1·63 (P < 0·001) at a comparable FT3 of 5·0 pm in the groups. Disparities were reflected by calculated deiodinase activity and remained significant even after accounting for confounding influences in a multivariable model. TSH, FT4 and FT3 each have their individual, but also interlocking roles to play in defining the overall patterns of thyroidal expression, regulation and metabolic activity. Equilibria typical of the healthy state are not invariant, but profoundly altered, for example, by L-T4 treatment. Consequently, this suggests the revisitation of strategies for treatment optimization. © 2014 John Wiley & Sons Ltd.

Determining Baseline Stress-Related Hormone Values in Large Cetaceans

DTIC Science & Technology

2015-09-30

individual whale. These reconstructed chemical profiles provided a unique window into stress-related hormone (cortisol, aldosterone , T3 and T4...stored under nitrogen at -30 °C. Stress-related hormone radioimmunoassay technique Cortisol, aldosterone , hormones thyroxine (T4) and...coefficients. These measurements will include all hormones ( aldosterone , T3, T4, and cortisol) as well as contaminants. The age trends for the 6 hormones will

Relationship between Total Homocysteine, Folic Acid, and Thyroid Hormones in Hypothyroid Dogs.

PubMed

Gołyński, M; Lutnicki, K; Krumrych, W; Szczepanik, M; Gołyńska, M; Wilkołek, P; Adamek, Ł; Sitkowski, Ł; Kurek, Ł

2017-09-01

Both elevated homocysteine and decreased folic acid concentrations are observed in human patients with hypothyroidism and can influence the development of numerous secondary disorders. The aim of the study was to assess total homocysteine concentration in serum and to examine its relationship with the concentration of folic acid and thyroid hormones (tT4 and fT4). Ten healthy and 19 hypothyroid client-owned dogs. Dogs with clinical signs of hypothyroidism had the diagnosis confirmed by additional tests. Total homocysteine, folic acid, total thyroxine, and free thyroxine concentrations in serum were evaluated. Hypothyroid dogs were diagnosed with increased homocysteine (median 22.20 μmol/L; range, 16.50-37.75) and decreased folic acid (median 20.62 nmol/L; range, 10.54-26.35) concentrations, as compared to healthy dogs (11.52 μmol/L; range, 10.00-16.65 and 30.68 nmol/L; range, 22.84-38.52, respectively). In sick dogs, total homocysteine was inversely correlated with folic acid (ρ = -0.47, P < 0.001), total thyroxine (ρ = -0.69, P = 0.0092), and free thyroxine (ρ = -0.56, P = 0.0302). Hypothyroidism in dogs causes hyperhomocysteinemia. Concomitant mild folic acid decrease in hypothyroid dogs might be as a result of hyperhomocysteinemia. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Determination of serum thyroxine enantiomers in patients by liquid chromatography with a chiral mobile phase.

PubMed

Wang, Rong; Jia, Zheng-Ping; Hu, Xiao-Li; Xu, Li-Ting; Li, Yong-Min; Chen, Li-Ren

2003-03-05

A chromatographic method for the separation and determination of D- and L-thyroxine enantiomers (D-, and L-T4) in human serum with a chiral ligand ion-exchange system using a chiral mobile phase additive and a silica column was established. An aqueous eluent containing L-proline (L-pro) sufficiently complexed copper II ions and triethylamine (TEA) was used. It was monitored with a UV detector. The separation was completed in 12 min. The method has acceptable sensitivity, precision and accuracy for analysis. The limit of detection and the limit of quantitation for both D- and L-T4 were 0.1 microg/ml and 0.8 microg/ml, respectively. Calibration curves were linear within 1-100 microg/ml; the mean correlation coefficients were r(D-T4)=0.9986 for D-T4 and r(L-T4)=0.9978 for L-T4. T4 enantiomers were separated on baseline under the optimum condition. L-T4 eluted before D-T4. The concentration of D-T4 and L-T4 in 45 thyroid patients serum (hyperthyroid, hypothyroid, thyroidectomy, goitre or thyroiditis) using HPLC was determined, those results showed that D,L-T4 concentration varied in different thyroid patient. Attention should be paid to this result in treating thyroid disease in the clinic. Copyright 2002 Elsevier Science B.V.

Stir bar sorptive extraction combined with high performance liquid chromatography-ultraviolet/inductively coupled plasma mass spectrometry for analysis of thyroxine in urine samples.

PubMed

Fan, Wenying; Mao, Xiangju; He, Man; Chen, Beibei; Hu, Bin

2013-11-29

tIn this work, polyethyleneglycol (PEG)/hydroxyl polydimethylsiloxane (OH-PDMS)/γ -mercaptopropyltrimethoxysilane (γ -MPTS) coated stir bar was prepared by sol–gel process and its extraction performance for the extraction of amphoteric thyroxines (3,3',5,5'-tetraiodothyronin, T(4); 3,3',5-triiodothyronine, T(3); reversed-3,3',5-triiodothyronine, rT(3)) and their metabolite (3,5-diiodothyronine,T2) was studied. The preparation reproducibility of PEG/OH-PDMS/γ -MPTS coated stir bar was investigated, and the relative standard deviations (RSDs) in the same batch and among different batches were 3.3–14.3% (n = 5) and 7.7–16.6% (n = 3), respectively. The prepared PEG/OH-PDMS/γ -MPTS coated stir bar could be reused for more than 20 times. Based on this fact, a novel method of stir bar sorptive extraction (SBSE) combined with high performance liquid chromatography (HPLC)-ultraviolet (UV)and HPLC-inductively coupled plasma mass spectrometry (ICP-MS) for the analysis of target thyroxinesin human urine samples was developed. The influencing factors of SBSE, such as sample pH, extraction time, stirring rate, salt effect, desorption solution and desorption time, were studied in detail, and the analytical performance of the proposed method was evaluated under the optimized conditions. The enrichment factors (EFs) of the developed method for four target thyroxines were in the range of 14.9–70.4(theoretical enrichment factor was 100). The RSDs were ranging from 4.0% to 13.8% for SBSE-HPLC-UV (c = 25 μg/L, n = 6) and from 3.7% to 6.1% for SBSE-HPLC-ICP-MS (c = 0.5 μg/L, n = 5). The linear range obtained by SBSE-HPLC-UV was 2–500 μg/L for T(2)and 5–500 μg/L for rT3, T(3)and T(4), with correlation coefficients (r) ranging from 0.9957 to 0.9998, respectively, while the linear range obtained by SBSE-HPLC-ICP-MS was 0.05–500 μg/L for T(2) and rT(3), 0.10–200 μg/L for T(3) and 0.05–200 μg/L for T(4)with r ranging from 0.9979 to 0.9998, respectively. The limits of detection (LODs) for the target thyroxines were 0.60–2.20 μg/L for SBSE-HPLC-UV and 0.0071–0.0355 μg/L SBSE-HPLC-ICP-MS, respectively. The developed method was applied for the determination of target thyroxines in urine samples, and the recovery for the spiking samples obtained by SBSE-HPLC-UV was in the range of 81.6–137.6% for human urine,while the recovery for the spiking urine samples obtained by SBSE-HPLC-ICP-MS were in the range of 72.0–121.5%.

Stability indicating validated HPLC method for quantification of levothyroxine with eight degradation peaks in the presence of excipients.

PubMed

Shah, R B; Bryant, A; Collier, J; Habib, M J; Khan, M A

2008-08-06

A simple, sensitive, accurate, and robust stability indicating analytical method is presented for identification, separation, and quantitation of l-thyroxine and eight degradation impurities with an internal standard. The method was used in the presence of commonly used formulation excipients such as butylated hydroxyanisole, povidone, crospovidone, croscarmellose sodium, mannitol, sucrose, acacia, lactose monohydrate, confectionary sugar, microcrystalline cellulose, sodium laurel sulfate, magnesium stearate, talc, and silicon dioxide. The two active thyroid hormones: 3,3',5,5'-tetra-iodo-l-thyronine (l-thyroxine-T4) and 3,3',5-tri-iodo-l-thyronine (T3) and degradation products including di-iodothyronine (T2), thyronine (T0), tyrosine (Tyr), di-iodotyrosine (DIT), mono-iodotyrosine (MIT), 3,3',5,5'-tetra-iodothyroacetic acid (T4AA) and 3,3',5-tri-iodothyroacetic acid (T3AA) were assayed by the current method. The separation of l-thyroxine and eight metabolites along with theophylline (internal standard) was achieved using a C18 column (25 degrees C) with a mobile phase of trifluoroacetic acid (0.1%, v/v, pH 3)-acetonitrile in gradient elution at 0.8 ml/min at 223 nm. The sample diluent was 0.01 M methanolic NaOH. Method was validated according to FDA, USP, and ICH guidelines for inter-day accuracy, precision, and robustness after checking performance with system suitability. Tyr (4.97 min), theophylline (9.09 min), MIT (9.55 min), DIT (11.37 min), T0 (11.63 min), T2 (14.47 min), T3 (16.29 min), T4 (17.60 min), T3AA (22.71 min), and T4AA (24.83 min) separated in a single chromatographic run. Linear relationship (r2>0.99) was observed between the peak area ratio and the concentrations for all of the compounds within the range of 2-20 microg/ml. The total time for analysis, equilibration and recovery was 40 min. The method was shown to separate well from commonly employed formulation excipients. Accuracy ranged from 95 to 105% for T4 and 90 to 110% for all other compounds. Precision was <2% for all the compounds. The method was found to be robust with minor changes in injection volume, flow rate, column temperature, and gradient ratio. Validation results indicated that the method shows satisfactory linearity, precision, accuracy, and ruggedness and also stress degradation studies indicated that the method can be used as stability indicating method for l-thyroxine in the presence of excipients.

Triclosan Alters Thyroid Hormone Homeostasis via Up-regulation of Hepatic Catabolism

EPA Science Inventory

Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) decreases serum thyroxine (T4) in the weanling rat. Scientific uncertainties include: by what mode of action (MOA) does triclosan decrease T4, and does triclosan induce hypothyroxinemia in dams and neonates? To test the hypothes...

Evidence of thyroxine formation following iodine administration in Sprague-Dawley rats

NASA Technical Reports Server (NTRS)

Thrall, K. D.; Sauer, R. L.; Bull, R. J.

1992-01-01

Iodine (I2) has been proposed to be used as a water disinfectant on the manned space station. Previous work has shown that subchronic administration of I2 to Sprague-Dawley rats in drinking water significantly increases plasma thyroxine/triiodothyronine (T4/T3) levels. This is not observed with iodide (I-) treatment. The present study addresses the possibility that I2 reacts with deiodinated T4 metabolites in the gastrointestinal tract to resynthesize T4. Incubation of diiodothyronine (T2), T3, or reverse T3 with I2 in phosphate-buffered saline resulted in the formation of T4 as measured by radioimmunoassay. Washes from the initial segments of the small intestine of the rat show that substrates are present that react with I2 to produce T4. Single oral doses of I2 to rats produced significant dose-related increases in serum T4 and decreases in T3 concentrations after 2 h. Administration of an equivalent dose of I- did not alter significantly plasma T4 concentrations. Higher concentrations of a radioactive substance that bound a T4-specific antibody are present in plasma of animals treated with 125I2 compared to 125I-. These data support the hypothesis that I2 reacts with metabolites of thyroid hormone in the gastrointestinal tract to resynthesize T4 and elevate its levels in blood.

Unusual Ratio between Free Thyroxine and Free Triiodothyronine in a Long-Lived Mole-Rat Species with Bimodal Ageing

PubMed Central

Henning, Yoshiyuki; Vole, Christiane; Begall, Sabine; Bens, Martin; Broecker-Preuss, Martina; Sahm, Arne; Szafranski, Karol; Burda, Hynek; Dammann, Philip

2014-01-01

Ansell's mole-rats (Fukomys anselli) are subterranean, long-lived rodents, which live in eusocial families, where the maximum lifespan of breeders is twice as long as that of non-breeders. Their metabolic rate is significantly lower than expected based on allometry, and their retinae show a high density of S-cone opsins. Both features may indicate naturally low thyroid hormone levels. In the present study, we sequenced several major components of the thyroid hormone pathways and analyzed free and total thyroxine and triiodothyronine in serum samples of breeding and non-breeding F. anselli to examine whether a) their thyroid hormone system shows any peculiarities on the genetic level, b) these animals have lower hormone levels compared to euthyroid rodents (rats and guinea pigs), and c) reproductive status, lifespan and free hormone levels are correlated. Genetic analyses confirmed that Ansell's mole-rats have a conserved thyroid hormone system as known from other mammalian species. Interspecific comparisons revealed that free thyroxine levels of F. anselli were about ten times lower than of guinea pigs and rats, whereas the free triiodothyronine levels, the main biologically active form, did not differ significantly amongst species. The resulting fT4:fT3 ratio is unusual for a mammal and potentially represents a case of natural hypothyroxinemia. Comparisons with total thyroxine levels suggest that mole-rats seem to possess two distinct mechanisms that work hand in hand to downregulate fT4 levels reliably. We could not find any correlation between free hormone levels and reproductive status, gender or weight. Free thyroxine may slightly increase with age, based on sub-significant evidence. Hence, thyroid hormones do not seem to explain the different ageing rates of breeders and non-breeders. Further research is required to investigate the regulatory mechanisms responsible for the unusual proportion of free thyroxine and free triiodothyronine. PMID:25409169

Unusual ratio between free thyroxine and free triiodothyronine in a long-lived mole-rat species with bimodal ageing.

PubMed

Henning, Yoshiyuki; Vole, Christiane; Begall, Sabine; Bens, Martin; Broecker-Preuss, Martina; Sahm, Arne; Szafranski, Karol; Burda, Hynek; Dammann, Philip

2014-01-01

Ansell's mole-rats (Fukomys anselli) are subterranean, long-lived rodents, which live in eusocial families, where the maximum lifespan of breeders is twice as long as that of non-breeders. Their metabolic rate is significantly lower than expected based on allometry, and their retinae show a high density of S-cone opsins. Both features may indicate naturally low thyroid hormone levels. In the present study, we sequenced several major components of the thyroid hormone pathways and analyzed free and total thyroxine and triiodothyronine in serum samples of breeding and non-breeding F. anselli to examine whether a) their thyroid hormone system shows any peculiarities on the genetic level, b) these animals have lower hormone levels compared to euthyroid rodents (rats and guinea pigs), and c) reproductive status, lifespan and free hormone levels are correlated. Genetic analyses confirmed that Ansell's mole-rats have a conserved thyroid hormone system as known from other mammalian species. Interspecific comparisons revealed that free thyroxine levels of F. anselli were about ten times lower than of guinea pigs and rats, whereas the free triiodothyronine levels, the main biologically active form, did not differ significantly amongst species. The resulting fT4:fT3 ratio is unusual for a mammal and potentially represents a case of natural hypothyroxinemia. Comparisons with total thyroxine levels suggest that mole-rats seem to possess two distinct mechanisms that work hand in hand to downregulate fT4 levels reliably. We could not find any correlation between free hormone levels and reproductive status, gender or weight. Free thyroxine may slightly increase with age, based on sub-significant evidence. Hence, thyroid hormones do not seem to explain the different ageing rates of breeders and non-breeders. Further research is required to investigate the regulatory mechanisms responsible for the unusual proportion of free thyroxine and free triiodothyronine.

Effects of prolonged fasting on plasma cortisol and TH in postweaned northern elephant seal pups

NASA Technical Reports Server (NTRS)

Ortiz, R. M.; Wade, C. E.; Ortiz, C. L.

2001-01-01

Northern elephant seal (Mirounga angustirostris) pups rely on the oxidation of fat stores as their primary source of energy during their 8- to 12-wk postweaning fast; however, potential endocrine mechanisms involved with this increased fat metabolism have yet to be examined. Therefore, 15 pups were serially blood sampled in the field during the first 7 wk of their postweaning fast to examine the changes in plasma concentrations of cortisol and thyroid hormones (TH), which are involved in fat metabolism in other mammals. Cortisol increased, indicating that it contributed to an increase in lipolysis. Increased total triiodothyronine (tT(3)) and thyroxine (tT(4)) may not reflect increased thyroid gland activity, but rather alterations in hormone metabolism. tT(3)-to-tT(4) ratio decreased, suggesting a decrease in thyroxine (T(4)) deiodination, whereas the negative correlation between total proteins and free T(4) suggests that the increase in free hormone is attributed to a decrease in binding globulins. Changes in TH are most similar to those observed during hibernation than starvation in mammals, suggesting that the metabolic adaptations to natural fasting are more similar to hibernation despite the fact these animals remain active throughout the fasting period.

Five-Year Follow-Up for Women With Subclinical Hypothyroidism in Pregnancy

PubMed Central

Shields, Beverley M.; Knight, Bridget A.; Hill, Anita V.; Hattersley, Andrew T.

2013-01-01

Context: Increasing numbers of women are being treated with l-thyroxine in pregnancy for mild thyroid dysfunction because of its association with impaired neuropsychological development in their offspring and other adverse obstetric outcomes. However, there are limited data to indicate whether treatment should be continued outside of pregnancy. Objectives: We aimed to determine whether subclinical hypothyroidism and maternal hypothyroxinemia resolve postdelivery. Design, Setting, and Participants: A total of 523 pregnant healthy women with no known thyroid disorders were recruited during routine antenatal care and provided blood samples at 28 weeks of pregnancy and at a mean of 4.9 years postpregnancy. Main Outcome Measures: TSH, free T4, free T3, and thyroid peroxidase antibody levels were measured in serum taken in pregnancy and at follow-up. Results: Subclinical hypothyroidism in pregnancy (TSH >3 mIU/L) was present in 65 of 523 (12.4%) women. Of these, 49 (75.4%) women had normal thyroid function postpregnancy; 16 of 65 (24.6%) had persistent high TSH (TSH >4.5 mIU/L postpregnancy) with 3 women receiving l-thyroxine treatment. A total of 44 of 523 (8.4%) women had isolated maternal hypothyroxinemia in pregnancy (free T4 <10th centile and TSH ≤3 mIU/L). Only 2 of 44 (4.5%) had TSH >4.5 mIU/L outside pregnancy. Of the women with subclinical hypothyroidism in pregnancy with antibody measurements available, those with thyroid peroxidase antibodies in pregnancy were more likely to have persistently elevated TSH or be receiving l-thyroxine replacement after pregnancy (6 of 7 [86%] vs 10 of 57 [18%], P < .001). Conclusions: The majority of cases of subclinical hypothyroidism in pregnancy are transient, so treatment with l-thyroxine in these patients should be reviewed because it may not be warranted after pregnancy. PMID:24217906

Type II iodothyronine deiodinase provides intracellular 3,5,3'-triiodothyronine to normal and regenerating mouse skeletal muscle.

PubMed

Marsili, Alessandro; Tang, Dan; Harney, John W; Singh, Prabhat; Zavacki, Ann Marie; Dentice, Monica; Salvatore, Domenico; Larsen, P Reed

2011-11-01

The FoxO3-dependent increase in type II deiodinase (D2), which converts the prohormone thyroxine (T(4)) to 3,5,3'-triiodothyronine (T(3)), is required for normal mouse skeletal muscle differentiation and regeneration. This implies a requirement for an increase in D2-generated intracellular T(3) under these conditions, which has not been directly demonstrated despite the presence of D2 activity in skeletal muscle. We directly show that D2-mediated T(4)-to-T(3) conversion increases during differentiation in C(2)C(12) myoblast and primary cultures of mouse neonatal skeletal muscle precursor cells, and that blockade of D2 eliminates this. In adult mice given (125)I-T(4) and (131)I-T(3), the intracellular (125)I-T(3)/(131)I-T(3) ratio is significantly higher than in serum in both the D2-expressing cerebral cortex and the skeletal muscle of wild-type, but not D2KO, mice. In D1-expressing liver and kidney, the (125)I-T(3)/(131)I-T(3) ratio does not differ from that in serum. Hypothyroidism increases D2 activity, and in agreement with this, the difference in (125)I-T(3)/(131)I-T(3) ratio is increased further in hypothyroid wild-type mice but not altered in the D2KO. Notably, in wild-type but not in D2KO mice, the muscle production of (125)I-T(3) is doubled after skeletal muscle injury. Thus, D2-mediated T(4)-to-T(3) conversion generates significant intracellular T(3) in normal mouse skeletal muscle, with the increased T(3) required for muscle regeneration being provided by increased D2 synthesis, not by T(3) from the circulation.

Type II iodothyronine deiodinase provides intracellular 3,5,3′-triiodothyronine to normal and regenerating mouse skeletal muscle

PubMed Central

Marsili, Alessandro; Tang, Dan; Harney, John W.; Singh, Prabhat; Zavacki, Ann Marie; Dentice, Monica; Salvatore, Domenico

2011-01-01

The FoxO3-dependent increase in type II deiodinase (D2), which converts the prohormone thyroxine (T4) to 3,5,3′-triiodothyronine (T3), is required for normal mouse skeletal muscle differentiation and regeneration. This implies a requirement for an increase in D2-generated intracellular T3 under these conditions, which has not been directly demonstrated despite the presence of D2 activity in skeletal muscle. We directly show that D2-mediated T4-to-T3 conversion increases during differentiation in C2C12 myoblast and primary cultures of mouse neonatal skeletal muscle precursor cells, and that blockade of D2 eliminates this. In adult mice given 125I-T4 and 131I-T3, the intracellular 125I-T3/131I-T3 ratio is significantly higher than in serum in both the D2-expressing cerebral cortex and the skeletal muscle of wild-type, but not D2KO, mice. In D1-expressing liver and kidney, the 125I-T3/131I-T3 ratio does not differ from that in serum. Hypothyroidism increases D2 activity, and in agreement with this, the difference in 125I-T3/131I-T3 ratio is increased further in hypothyroid wild-type mice but not altered in the D2KO. Notably, in wild-type but not in D2KO mice, the muscle production of 125I-T3 is doubled after skeletal muscle injury. Thus, D2-mediated T4-to-T3 conversion generates significant intracellular T3 in normal mouse skeletal muscle, with the increased T3 required for muscle regeneration being provided by increased D2 synthesis, not by T3 from the circulation. PMID:21771965

Thyroxine to triiodothyronine hyperconversion thyrotoxicosis in patients with large metastases of follicular thyroid carcinoma.

PubMed

Takano, Toru; Miyauchi, Akira; Ito, Yasuhiro; Amino, Nobuyuki

2006-06-01

We experienced two cases of follicular thyroid carcinoma with distant metastases, which showed high levels of free triiodothyronine (T(3)) while free thyroxine (T(4)) levels remained in the low or normal range. In this report, we described the detail of these cases and examined the cause of T(3) thyrotoxicosis. In one of the cases, quantitative measurement of types I and II iodothyronine deiodinase mRNAs was performed using a surgically dissected tissue from the primary tumor and a distant metastasis. In the both tissues, types I and II iodothyronine deiodinase mRNAs were expressed in the same level as in the normal thyroid tissues. These results suggest that T(3) thyrotoxicosis in our patients was caused by hyperconversion of administered levothyroxine to T(3). In the follow-up of patients with distant metastases of follicular carcinoma, not only free T(4), but also free T(3) should be tested to avoid the excessive administration of levothyroxine.

Dissociation between plasma concentrations of thyroxine and insulin-like growth factor-I.

PubMed

Dauncey, M J; Morovat, A; Rudd, B T; Shakespear, R A

1990-09-01

The relation between plasma concentrations of thyroxine (T4) and insulin-like growth factor-I (IGF-I) has been examined in young, growing pigs under controlled conditions of energy intake. Compared with euthyroid controls, plasma levels of IGF-I were significantly elevated (P less than 0.005) both in hypothyroid animals on the same food intake and in hyperthyroid animals on double the food intake. There was however no increase in IGF-I in a hyperthyroid group on the control level of intake. Contrary to previous reports in which energy intake was not controlled, it is concluded that there is no simple correlation between plasma concentrations of T4 and IGF-I.

Differences in primary cellular factors influencing the metabolism and distribution of 3,5,3′-L-triiodothyronine and L-thyroxine

PubMed Central

Oppenheimer, Jack H.; Schwartz, Harold L.; Shapiro, Harvey C.; Bernstein, Gerald; Surks, Martin I.

1970-01-01

Administration of phenobarbital, which acts exclusively on cellular sites, results in an augmentation of the liver/plasma concentration ratio of L-thyroxine (T4) in rats but no change in the liver/plasma concentration ratio of L-triiodothyronine (T3). Whereas phenobarbital stimulates the fecal clearance rate both of T3 and T4, it increases the deiodinative clearance rate of T4 only. These findings suggest basic differences in the cellular metabolism of T3 and T4. Further evidence pointing to cellular differences was obtained from a comparison of the distribution and metabolism of these hormones with appropriate corrections for the effect of differential plasma binding. The percentage of total exchangeable cellular T4 within the liver (28.5) is significantly greater than the corresponding percentage of exchangeable cellular T3 within this organ (12.3). Extrahepatic tissues bind T3 twice as firmly as T4. The cellular metabolic clearance rate (= free hormone clearance rate) of T3 exceeds that of T4 by a factor 1.8 in the rat. The corresponding ratio in man, 2.4, was determined by noncompartmental analysis of turnover studies in four individuals after the simultaneous injection of T4-125I and T3-131I. The greater cellular metabolic clearance rate of T3 both in rat and man may be related to the higher specific hormonal potency of this iodothyronine. PMID:5441537

The colloidal thyroxine (T4) ring as a novel biomarker of perchlorate exposure in the African clawed frog Xenopus laevis

USGS Publications Warehouse

Hu, F.; Sharma, Bibek; Mukhi, S.; Patino, R.; Carr, J.A.

2006-01-01

The purpose of this study was to determine if changes in colloidal thyroxine (T4) immunoreactivity can be used as a biomarker of perchlorate exposure in amphibian thyroid tissue. Larval African clawed frogs (Xenopus laevis) were exposed to 0, 1, 8, 93, and 1131 ??g perchlorate/l for 38 and 69 days to cover the normal period of larval development and metamorphosis. The results of this study confirmed the presence of an immunoreactive colloidal T4 ring in thyroid follicles of X. laevis and demonstrated that the intensity of this ring is reduced in a concentration-dependent manner by perchlorate exposure. The smallest effective concentration of perchlorate capable of significantly reducing colloidal T4 ring intensity was 8 ??g perchlorate/l. The intensity of the immunoreactive colloidal T4 ring is a more sensitive biomarker of perchlorate exposure than changes in hind limb length, forelimb emergence, tail resorption, thyrocyte hypertrophy, or colloid depletion. We conclude that the colloidal T4 ring can be used as a sensitive biomarker of perchlorate-induced thyroid disruption in amphibians. ?? Copyright 2006 Oxford University Press.

Effect of subclinical hypothyroidism on the skeletal system and improvement with short-term thyroxine therapy.

PubMed

Gao, Cuixia; Wang, Yu; Li, Tingting; Huang, Jing; Tian, Limin

2017-10-27

The purpose of the study was to observe changes in the skeletal system of rats with subclinical hypothyroidism (SCH) and to determine whether L-thyroxine (L-T4) administration suppresses those changes. Sixty male Wistar rats were randomly divided into control, SCH, and SCH+T4 groups. SCH was induced in rats by administration of methimazole (MMI), and rats in the SCH+T4 group were treated with L-T4 after 45 days of MMI administration. The SCH group had higher thyroid-stimulating hormone (TSH) level than the control and SCH+T4 groups. There were no differences in serum thyroid hormone (FT4 and FT3) levels among the three groups. Bone mineral density; serum levels of BALP and TRACP-5b, two bone metabolic markers; and the biomechanical properties of the femurs were lower in the SCH group than in the control group. After L-T4 treatment, serum BALP and TRACP-5b levels and the femur biomechanical properties were higher in the SCH+T4 than the SCH group. Histopathological examination revealed damage to the structure of the femur trabecular bone network in rats with SCH, and L-T4 treatment improved this condition to some extent. These findings demonstrate that L-T4 treatment ameliorates the destructive effects of SCH on the skeletal system in rats.

ANIMAL PHYSIOLOGY. Exceptionally low daily energy expenditure in the bamboo-eating giant panda.

PubMed

Nie, Yonggang; Speakman, John R; Wu, Qi; Zhang, Chenglin; Hu, Yibo; Xia, Maohua; Yan, Li; Hambly, Catherine; Wang, Lu; Wei, Wei; Zhang, Jinguo; Wei, Fuwen

2015-07-10

The carnivoran giant panda has a specialized bamboo diet, to which its alimentary tract is poorly adapted. Measurements of daily energy expenditure across five captive and three wild pandas averaged 5.2 megajoules (MJ)/day, only 37.7% of the predicted value (13.8 MJ/day). For the wild pandas, the mean was 6.2 MJ/day, or 45% of the mammalian expectation. Pandas achieve this exceptionally low expenditure in part by reduced sizes of several vital organs and low physical activity. In addition, circulating levels of thyroid hormones thyroxine (T4) and triiodothyronine (T3) averaged 46.9 and 64%, respectively, of the levels expected for a eutherian mammal of comparable size. A giant panda-unique mutation in the DUOX2 gene, critical for thyroid hormone synthesis, might explain these low thyroid hormone levels. A combination of morphological, behavioral, physiological, and genetic adaptations, leading to low energy expenditure, likely enables giant pandas to survive on a bamboo diet. Copyright © 2015, American Association for the Advancement of Science.

Montmorillonite ameliorates hyperthyroidism of rats and mice attributed to its adsorptive effect.

PubMed

Cai, Yan; Meng, Xin-fang; Cao, Yong-xiao; Lu, Hua; Zhu, Shao-fei; Zhou, Liang-zhen

2006-12-03

The present study aims to evaluate the adsorbing effect of montmorillonite on thyroid hormone in the entero-hepatic circulation. The concentration of thyroid hormone in the serum of hyperthyroidism model rats and in solution was measured by radioimmunoassay and ultraviolet spectrometry, respectively. The body weight, temperature, and consumption of food and water were observed in hyperthyroidism model rats. Furthermore, hypoxia tolerance, sodium-pentobarbital-induced sleep time, spontaneous activities were measured on hyperthyroidism model mice after being treated with montmorillonite. Results showed that montmorillonite adsorbed thyroxin (T(4)) and triiodothyronine (T(3)) in vitro. Montmorillonite at dosage of 1.0 g/kg and 0.3 g/kg decreased thyroid hormone levels on hyperthyroidism model rats; Montmorillonite (2.0 g/kg and 0.6 g/kg) prolonged the sleep time, improved the hypoxia tolerant capacity and reduced the spontaneous activities of the hyperthyroidism model mice. These results suggest montmorillonite has anti-hyperthyroidism effect attributed to its adsorptive effect.

Effects of thyroxine replacement on endothelial function and carotid artery intima-media thickness in female patients with mild subclinical hypothyroidism

PubMed Central

Cabral, Monica Dias; Teixeira, Patricia; Soares, Debora; Leite, Sandra; Salles, Elizabeth; Waisman, Mario

2011-01-01

BACKGROUND: Previous studies have suggested an association between subclinical hypothyroidism and coronary artery disease that could be related to changes in serum lipids or endothelial dysfunction. METHODS: Thirty-two female subclinical hypothyroidism patients were randomly assigned to 12 months of L-thyroxine replacement or no treatment. Endothelial function was measured by the flow-mediated vasodilatation of the brachial artery, as well as mean carotid artery intima-media thickness, and lipid profiles were studied at baseline and after 12 months of follow-up. RESULTS: The mean (±SD) serum thyroid-stimulating hormone levels in the L-thyroxine replacement and control groups were 6.09±1.32 and 6.27±1.39 µUI/ml, respectively. No relationship between carotid artery intima-media thickness or brachial flow-mediated vasodilatation and free T4 and serum thyroid-stimulating hormone was found. The median L-T4 dose was 44.23±18.13 µg/day. After 12 months, there was a significant decrease in the flow-mediated vasodilatation in the subclinical hypothyroidism control group (before: 17.33±7.88 to after: 13.1±4.75%, p = 0.03), but there were no significant differences in flow-mediated vasodilatation in the L-thyroxine treated group (before: 16.81±7.0 to after: 18.52±7.44%, p = 0.39). We did not find any significant change in mean carotid intima-media thickness after 12 months of L-thyroxine treatment. CONCLUSION: Replacement therapy prevents a decline in flow-mediated vasodilatation with continuation of the subclinical hypothyroidism state. Large prospective multicenter placebo-controlled trials are necessary to investigate endothelial physiology further in subclinical hypothyroidism patients and to define the role of L-thyroxine therapy in improving endothelial function in these patients. PMID:21915478

A randomized, open-label, crossover study comparing the effects of oral versus transdermal estrogen therapy on serum androgens, thyroid hormones, and adrenal hormones in naturally menopausal women.

PubMed

Shifren, Jan L; Desindes, Sophie; McIlwain, Marilyn; Doros, Gheorghe; Mazer, Norman A

2007-01-01

To compare the changes induced by oral versus transdermal estrogen therapy on the total and free serum concentrations of testosterone (T), thyroxine (T4), and cortisol (C) and the concentrations of their serum binding globulins sex hormone-binding globulin, thyroxine-binding globulin, and cortisol-binding globulin in naturally menopausal women. Randomized, open-label, crossover. Interventions included a 6-week withdrawal from previous hormone therapy (baseline), followed in randomized order by 12 weeks of oral conjugated equine estrogens (CEE) (0.625 mg/d) and 12 weeks of transdermal estradiol (TD E2) (0.05 mg/d), with oral micronized progesterone (100 mg/d) given continuously during both transdermal estrogen therapy regimens. Twenty-seven women were enrolled in the study, and 25 completed both treatment periods. The mean(SD) percentage changes from baseline of sex hormone-binding globulin, total T, and free T with oral CEE were +132.1% (74.5%), +16.4% (43.8%), and -32.7% (25.9%), respectively, versus +12.0% (25.1%), +1.2% (43.7%), and +1.0% (45.0%) with TD E2. The mean (SD) percentage changes of thyroxine-binding globulin, total T4, and free T4 with oral CEE were +39.9% (20.1%), +28.4% (29.2%), and -10.4% (22.3%), respectively, versus +0.4% (11.1%), -0.7% (16.5%), and +0.2% (26.6%) with TD E2. The mean (SD) percentage changes of cortisol-binding globulin, total C, and free C with oral CEE were +18.0% (19.5%), +29.2% (46.3%), and +50.4% (126.5%), respectively, versus -2.2% (11.3%), -6.7% (30.8%), and +1.8% (77.1%) with TD E2. Concentrations of all hormones and binding globulins were significantly different (P < or = 0.003) during administration of oral versus transdermal estrogen therapy, except for free T4 and free C. Compared with oral CEE, TD E2 exerts minimal effects on the total and free concentrations of T, T4, and C and their binding proteins.

Glycosyltransferase Function in Core 2-Type Protein O Glycosylation▿

PubMed Central

Stone, Erica L.; Ismail, Mohd Nazri; Lee, Seung Ho; Luu, Ying; Ramirez, Kevin; Haslam, Stuart M.; Ho, Samuel B.; Dell, Anne; Fukuda, Minoru; Marth, Jamey D.

2009-01-01

Three glycosyltransferases have been identified in mammals that can initiate core 2 protein O glycosylation. Core 2 O-glycans are abundant among glycoproteins but, to date, few functions for these structures have been identified. To investigate the biological roles of core 2 O-glycans, we produced and characterized mice deficient in one or more of the three known glycosyltransferases that generate core 2 O-glycans (C2GnT1, C2GnT2, and C2GnT3). A role for C2GnT1 in selectin ligand formation has been described. We now report that C2GnT2 deficiency impaired the mucosal barrier and increased susceptibility to colitis. C2GnT2 deficiency also reduced immunoglobulin abundance and resulted in the loss of all core 4 O-glycan biosynthetic activity. In contrast, the absence of C2GnT3 altered behavior linked to reduced thyroxine levels in circulation. Remarkably, elimination of all three C2GnTs was permissive of viability and fertility. Core 2 O-glycan structures were reduced among tissues from individual C2GnT deficiencies and completely absent from triply deficient mice. C2GnT deficiency also induced alterations in I-branching, core 1 O-glycan formation, and O mannosylation. Although the absence of C2GnT and C4GnT activities is tolerable in vivo, core 2 O glycosylation exerts a significant influence on O-glycan biosynthesis and is important in multiple physiological processes. PMID:19349303

Increased Requirement of Replacement Doses of Levothyroxine Caused by Liver Cirrhosis.

PubMed

Benvenga, Salvatore; Capodicasa, Giovanni; Perelli, Sarah; Ferrari, Silvia Martina; Fallahi, Poupak; Antonelli, Alessandro

2018-01-01

Since hypothyroidism is a fairly common dysfunction, levothyroxine (L-T4) is one of the most prescribed medications. Approximately 70% of the administered L-T4 dose is absorbed. The absorption process takes place in the small intestine. Some disorders of the digestive system and some medicines, supplements, and drinks cause L-T4 malabsorption, resulting in failure of serum TSH to be normal. Only rarely liver cirrhosis is mentioned as causing L-T4 malabsorption. In this study, we report increased requirement of daily doses of l-thyroxine in two patients with the atrophic variant of Hashimoto's thyroiditis and liver cirrhosis. In one patient, this increased requirement could have been contributed by the increased serum levels of the estrogen-dependent thyroxine-binding globulin (TBG), which is the major plasma carrier of thyroid hormones. In the other patient, we switched from tablet L-T4 to liquid L-T4 at the same daily dose. Normalization of TSH levels was achieved, but TSH increased again when she returned to tablet L-T4. Liver cirrhosis can cause increased L-T4 requirements. In addition to impaired bile secretion, the mechanism could be increased serum TBG. A similar increased requirement of L-T4 is observed in other situations characterized by elevation of serum TBG. Because of better intestinal absorption, L-T4 oral liquid formulation is able to circumvent the increased need of L-T4 in these patients.

The role of hepatic mitochondria in the regulation of glucose metabolism in BHE rats

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

Kim, M.J.C.

The interacting effects of dietary fat source and thyroxine treatment on the hepatic mitochondrial function and glucose metabolism were studied. In the first study, three different sources of dietary fatty acids and thyroxine treatment were used to investigate the hepatic mitochondrial thermotropic behavior in two strains of rat. The NIDDM BHE and Sprague-Dawley rats were used. Feeding coconut oil increased serum T{sub 4} levels and T{sub 4} treatment increased serum T{sub 3} levels in the BHE rats. In the mitochondria from BHE rats fed coconut oil and treated with T{sub 4}, the transition temperature disappeared due to a decoupling ofmore » succinate supported respiration. This was not observed in the Sprague-Dawley rats. In the second study, two different sources of dietary fat and T{sub 4} treatment were used to investigate hepatic mitochondrial function. Coconut oil feeding increased Ca{sup ++}Mg{sup ++}ATPase and Mg{sup ++}ATPase. T{sub 4} treatment had potentiated this effect. T{sub 4} increased the malate-aspartate shuttle and {alpha}-glycerophosphate shuttle activities. In the third study, the glucose turnover rate from D-({sup 14}C-U)/(6-{sup 3}H)-glucose and gluconeogeneis from L-({sup 14}C-U)-alanine was examined. Dietary fat or T{sub 4} did not affect the glucose mass. T{sub 4} increased the irreversible fractional glucose turnover rate.« less

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

Pharmaceutical studies of levothyroxine sodium hydrate suppository provided as a hospital preparation.

PubMed

Hamada, Yuhei; Masuda, Kazushi; Okubo, Masato; Nakasa, Hiromitsu; Sekine, Yuko; Ishii, Itsuko

2015-01-01

The levothyroxine sodium hydrate suppository (L-T4-suppository) is provided as a hospital preparation for the treatment of hypothyroid patients with dysphagia in Japan because only oral preparations of levothyroxine sodium (L-T4) are approved for the treatment of hypothyroidism. However, it has been found that serum thyroxine and triiodothyronine levels do not increase as expected with the hospital preparation, requiring a higher dosage of L-T4 in the L-T4-suppository than in the oral preparations. In this study, to determine an effective thyroid gland hormone-replacement therapy for patients with dysphagia, the pharmaceutical properties of the L-T4-suppository were investigated. Suppositories containing 300 µg L-T4 in a base of Witepsol H-15 and Witepsol E-75 (ratio of 1 : 1) were prepared according to Chiba University Hospital's protocol. Content uniformity, stability, and suppository release were tested. The L-T4-suppository had uniform weight and content. The content and release property were stable over 90 d when the L-T4-suppository was stored at 4 °C and protected from light. The release rate of L-T4 increased as pH increased. However, no L-T4 was released below pH 7.2. The release rate of L-T4 decreased as temperature decreased. These findings suggest that the low level of release of L-T4 in the rectum under physiological conditions may be the cause of the low serum thyroxine and triiodothyronine levels following L-T4-suppository administration.

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.

Effect of Propranolol on Thyroxine-Induced Changes in Body Temperature and Metabolism During Exercise in Dogs

NASA Technical Reports Server (NTRS)

Kaciuba-Uscilko, Hanna; Brzezinska, Zofia; Greenleaf, John E.

1976-01-01

Effects of thyroxine on temperature and metabolism during exercise were studied in dogs after beta-adrenergic blockade. Dogs performed 60 min treadmill exercise of moderate intensity 5 and 72 h following thyroxine injected s. c. in a single dose of 0.1 mg/kg b.w. Thyroxine increased significantly the lipolytic response to exercise as well as blood lactate (LA) concentrations and rectal temperature (T(sub re)) during exercise as early as 5 h following the hormone administration. The changes became more pronounced 72 h after the injection. At rest T(sub re), blood FFA (free fatty acid) and LA levels in the thyroxine-treated dogs did not differ from the control values, and blood glucose was slightly, but significantly higher. Propranolol given intravenously in a dose of 0.25 mg/kg at 30 min of the exercise performed 72 h following thyroxine injection abolished the plasma FFA rise, and inhibited to a certain extent increases in T(sub re) and blood LA concentrations during the next 30 min of exercise.

Selective affinity labeling of a 27-kDa integral membrane protein in rat liver and kidney with N-bromoacetyl derivatives of L-thyroxine and 3,5,3'-triiodo-L-thyronine.

PubMed

Köhrle, J; Rasmussen, U B; Rokos, H; Leonard, J L; Hesch, R D

1990-04-15

125I-Labeled N-bromoacetyl derivatives of L-thyroxine and L-triiodothyronine were used as alkylating affinity labels to identify rat liver and kidney microsomal membrane proteins which specifically bind thyroid hormones. Affinity label incorporation was analyzed by ethanol precipitation and individual affinity labeled proteins were identified by autoradiography after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Six to eight membrane proteins ranging in size from 17 to 84 kDa were affinity labeled by both bromoacetyl-L-thyroxine (BrAcT4) and bromoacetyl-L-triiodothyronine (BrAcT3). Affinity labeling was time- and temperature-dependent, and both reduced dithiols and detergents increased affinity labeling, predominantly in a 27-kDa protein(s). Up to 80% of the affinity label was associated with a 27-kDa protein (p27) under optimal conditions. Affinity labeling of p27 by 0.4 nM BrAc[125I]L-T4 was blocked by 0.1 microM of the alkylating ligands BrAcT4, BrAcT3, or 100 microM iodoacetate, by 10 microM concentrations of the non-alkylating, reversible ligands N-acetyl-L-thyroxine, 3,3',5'-triiodothyronine, 3,5-diiodosalicylate, and EMD 21388, a T4-antagonistic flavonoid. Neither 10 microM L-T4, nor 10 microM N-acetyltriiodothyronine or 10 microM L-triiodothyronine blocked affinity labeling of p27 or other affinity labeled bands. Affinity labeling of a 17-kDa band was partially inhibited by excess of the alkylating ligands BrAcT4, BrAcT3, and iodoacetate, but labeling of other minor bands was not blocked by excess of the competitors. BrAc[125I]T4 yielded higher affinity label incorporation than BrAc[125I]T3, although similar banding patterns were observed, except that BrAcT3 affinity labeled more intensely a 58,000-Da band in liver and a 53,000-55,000-Da band in kidney. The pattern of other affinity labeled proteins with p27 as the predominant band was similar in liver and kidney. Peptide mapping of affinity labeled p27 and p55 bands by chemical cleavage and protease fragmentation revealed no common bands excluding that p27 is a degradation product of p55. These data indicate that N-bromoacetyl derivatives of T4 and T3 affinity label a limited but similar constellation of membrane proteins with BrAcT4 incorporation greater than that of BrAcT3. One membrane protein (p27) of low abundance (2-5 pmol/mg microsomal protein) with a reactive sulfhydryl group is selectively labeled under conditions identical to those used to measure thyroid hormone 5'-deiodination. Only p27 showed differential affinity labeling in the presence of noncovalently bound inhibitors or substrates on 5'-deiodinase suggesting that p27 is likely to be a component of type I 5'-deiodinase in rat liver and kidney.

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

PubMed Central

St Aubin, D J

1987-01-01

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

Altered intestinal absorption of L-thyroxine caused by coffee.

PubMed

Benvenga, Salvatore; Bartolone, Luigi; Pappalardo, Maria Angela; Russo, Antonia; Lapa, Daniela; Giorgianni, Grazia; Saraceno, Giovanna; Trimarchi, Francesco

2008-03-01

To report eight case histories, and in vivo and in vitro studies showing coffee's potential to impair thyroxine (T4) intestinal absorption. Of eight women with inappropriately high or nonsuppressed thyroid-stimulating hormone (TSH) when T4 was swallowed with coffee/espresso, six consented to the evaluation of their T4 intestinal absorption. This in vivo test was also administered to nine volunteers. In three separate tests, two 100 microg T4 tablets were swallowed with coffee, water, or water followed, 60 minutes later, by coffee. Serum T4 was assayed over the 4-hour period of the test. Two patients and two volunteers also agreed on having tested the intestinal absorption of T4 swallowed with solubilized dietary fibers. In the in vitro studies, classical recovery tests on known concentrations of T4 were performed in the presence of saline, coffee, or known T4 sequestrants (dietary fibers, aluminium hydroxide, and sucralfate). For the in vivo test, average and peak incremental rise of serum T4 (AIRST4 and PIRST4), time of maximal incremental rise of serum T4 (TMIRST4), and area under the curve (AUC) were determined. In patients and volunteers, the four outcome measures were similar in the water and water + coffee tests. In patients and volunteers, compared to water, coffee lowered AIRST4 (by 36% and 29%), PIRST4 (by 30% and 19%), and AUC (by 36% and 27%) and delayed TMIRST4 (by 38 and 43 minutes); bran was a superior interferer. In the in vitro studies, coffee was weaker than known T4 sequestrants. Coffee should be added to the list of interferers of T4 intestinal absorption, and T4 to the list of compounds whose absorption is affected by coffee.

Differences in hypothalamic type 2 deiodinase ubiquitination explain localized sensitivity to thyroxine

PubMed Central

Werneck de Castro, Joao Pedro; Fonseca, Tatiana L.; Ueta, Cintia B.; McAninch, Elizabeth A.; Abdalla, Sherine; Wittmann, Gabor; Lechan, Ronald M.; Gereben, Balazs; Bianco, Antonio C.

2015-01-01

The current treatment for patients with hypothyroidism is levothyroxine (L-T4) along with normalization of serum thyroid-stimulating hormone (TSH). However, normalization of serum TSH with L-T4 monotherapy results in relatively low serum 3,5,3′-triiodothyronine (T3) and high serum thyroxine/T3 (T4/T3) ratio. In the hypothalamus-pituitary dyad as well as the rest of the brain, the majority of T3 present is generated locally by T4 deiodination via the type 2 deiodinase (D2); this pathway is self-limited by ubiquitination of D2 by the ubiquitin ligase WSB-1. Here, we determined that tissue-specific differences in D2 ubiquitination account for the high T4/T3 serum ratio in adult thyroidectomized (Tx) rats chronically implanted with subcutaneous L-T4 pellets. While L-T4 administration decreased whole-body D2-dependent T4 conversion to T3, D2 activity in the hypothalamus was only minimally affected by L-T4. In vivo studies in mice harboring an astrocyte-specific Wsb1 deletion as well as in vitro analysis of D2 ubiquitination driven by different tissue extracts indicated that D2 ubiquitination in the hypothalamus is relatively less. As a result, in contrast to other D2-expressing tissues, the hypothalamus is wired to have increased sensitivity to T4. These studies reveal that tissue-specific differences in D2 ubiquitination are an inherent property of the TRH/TSH feedback mechanism and indicate that only constant delivery of L-T4 and L-T3 fully normalizes T3-dependent metabolic markers and gene expression profiles in Tx rats. PMID:25555216

Total and free thyroxine and triiodothyronine: Measurement discrepancies, particularly in inpatients

PubMed Central

Jonklaas, Jacqueline; Sathasivam, Anpalakan; Wang, Hong; Gu, Jianghong; Burman, Kenneth D.; Soldin, Steven J.

2014-01-01

Objective We compared the performance of tandem mass spectrometry versus immunoassay for measuring thyroid hormones in a diverse group of inpatients and outpatients. Methods Thyroxine (T4), triiodothyronine (T3), free thyroxine (FT4), and free triiodothyronine (FT3) were measured by liquid chromatography tandem mass spectrometry and immunoassay in 100 patients and the two assays were compared. Results T4 and T3 values measured by the two different assays correlated well with each other (r =0.91–0.95). However, the correlation was less good at the extremes (r = 0.51–0.75). FT4 and FT3 concentrations measured by the two assays correlated less well with each other (r = 0.75 and 0.50 respectively). The studied analytes had poor inverse correlation with the log-transformed TSH values (r = −0.22–0.51) in the population as a whole. The strongest correlations were seen in the groups of outpatients (r = −0.25–0.61). The weakest degree of correlation was noted in the inpatient group, with many correlations actually being positive. Conclusion The worst between-assay correlation was demonstrated at low and high hormone concentrations, in the very concentration ranges where accurate assay performance is typically most clinically important. Based on the lesser susceptibility of mass spectrometry to interferences from conditions such as binding protein abnormalities, we speculate that mass spectrometry better reflects the clinical situation. In this mixed population of inpatients and outpatients, we also note failure of assays to conform to the anticipated inverse linear relationship between thyroid hormones and log-transformed TSH. PMID:24936679

Pharmacokinetics of total thyroxine after repeated oral administration of levothyroxine solution and its clinical efficacy in hypothyroid dogs.

PubMed

van Dijl, I C; Le Traon, G; van de Meulengraaf, B D A M; Burgaud, S; Horspool, L J I; Kooistra, H S

2014-01-01

Oral levothyroxine (l-T4 ) supplementation is commonly used to treat hypothyroid dogs. Investigate the plasma profile and pharmacokinetics of total thyroxine (tT4 ) after PO administration of a l-T4 solution and its clinical efficacy in hypothyroid dogs. Ten dogs with naturally occurring hypothyroidism. After hypothyroidism diagnosis and supplementation with l-T4 solution PO q24h at 20 μg/kg BW for minimum 4 weeks, the plasma profile and pharmacokinetics of tT4 were determined over 34 hours and the clinical condition of the dogs was evaluated. Before dosing for pharmacokinetic evaluation, mean tT4 concentration was 23 ± 9 nmol/L. l-T4 was absorbed rapidly (tmax , 5 hours), reaching a mean maximal tT4 concentration of 56 ± 11 nmol/L. The apparent terminal half-life was 11.8 hours. Clinical signs of hypothyroidism improved or resolved in all dogs after 4 weeks of treatment. The dosage of 20 μg/kg PO q24h was judged appropriate in 5 dogs, and 4 dogs required slight increases (9-16%). Twice daily treatment, with a 30% increase in dosage, was necessary for 1 dog. The pharmacokinetics of l-T4 in hypothyroid dogs was similar to that reported in healthy euthyroid dogs. Clinical and hormonal responses to l-T4 solution were rapid in all dogs. The starting dosage of 20 μg/kg PO q24h was suitable for maintenance supplementation in 50% of the dogs, minor dosage modification was required in 4 other dogs, and treatment q12h was required in 1 dog. Copyright © 2014 by the American College of Veterinary Internal Medicine.

The concentration of iodine in horse serum and its relationship with thyroxin concentration by geological difference.

PubMed

Mochizuki, Mariko; Hayakawa, Noriyuki; Minowa, Fumiko; Saito, Akihiro; Ishioka, Katsumi; Ueda, Fukiko; Okubo, Kimihiro; Tazaki, Hiroyuki

2016-04-01

In this study, iodine and thyroxin (T4) concentrations in the serum of 69 horses were investigated. Higher iodine concentrations were obtained from the horses housed in Chiba Prefecture. In contrast, T4 concentrations of horses at Shizuoka Prefecture were higher than those of horses at Chiba Prefecture. There was a significant correlation (r = 0.643, P < 0.001) between the iodine and T4 concentrations of horses at Saitama and Shizuoka prefectures. Although a significant correlation (r = 0.794, P < 0.001) was also observed in the investigation of all horses at Chiba Prefecture, the distribution area of the data was separated from the data of horses housed in Saitama and Shizuoka prefectures. A higher iodine concentration in the environment is expected in the sampling area at Chiba Prefecture. Thus, it was suggested that the concentrations of iodine in the serum of horses are influenced by geological differences. It was thought that equine serum is a useful sample for monitoring.

Effect of recombinant human thyroid stimulating hormone on serum thyroxin and thyroid scintigraphy in euthyroid cats.

PubMed

van Hoek, Ingrid M; Peremans, Kathelijne; Vandermeulen, Eva; Duchateau, Luc; Gommeren, Kris; Daminet, Sylvie

2009-04-01

This study investigated the thyroidal response to administration of recombinant human thyroid stimulating hormone (rhTSH) by means of serum total thyroxine (TT(4)) concentration and pertechnetate uptake by the thyroid gland in six healthy euthyroid spayed female cats. A pertechnetate scan was performed on day 1 to calculate thyroid/salivary gland (T/S) uptake ratio. On day 3, 25 microg rhTSH was injected intravenously. Six hours later the thyroid scan was repeated as on day 1. Blood was drawn for serum TT(4) measurement prior to injection of rhTSH and performance of the pertechnetate scan. Statistically significant differences in mean serum TT(4) concentration, T/S uptake ratio before and 6h after rhTSH administration and T/S uptake ratio between left and right lobes were noted. We can conclude that 25 microg rhTSH increases pertechnetate uptake in the thyroid glands of cats, this should be taken into account when thyroid scintigraphy after rhTSH administration is interpreted.

Disruption of thyroxine and sex hormones by 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (DBE-DBCH) in American kestrels (Falco sparverius) and associations with reproductive and behavioral changes.

PubMed

Marteinson, Sarah C; Palace, Vince; Letcher, Robert J; Fernie, Kim J

2017-04-01

1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (DBE-DBCH - formerly TBECH) is an emerging brominated flame retardant (BFR) pollutant with androgen potentiating ability and other endocrine disrupting effects in birds and fish. The objectives of this study were to determine the effects of exposure to environmentally-relevant levels of DBE-DBCH on circulating levels of thyroid and sex steroid hormones in American kestrels, and if hormonal concentrations were related to previously reported changes in reproductive success and courtship behaviors. Sixteen kestrel pairs were exposed to 0.239ng β-DBE-DBCH/g kestrel/day by diet, based on concentrations in wild bird eggs, from 4 weeks before pairing until the chicks hatched (mean 82 d), and were compared with vehicle-only-exposed control pairs (n=15). As previously reported, DBE-DBCH concentrations were not detected in tissue or eggs of these birds, nor were any potential metabolites, despite the low method limits of detection (≤0.4ng/g wet weight), suggesting it may be rapidly metabolized and/or eliminated by the kestrels. Nevertheless, exposed kestrels demonstrated changes in reproduction and behavior, indicating an effect from exposure. During early breeding, males were sampled at multiple time points at pairing and during courtship and incubation; females were blood sampled at pairing only; both sexes were sampled at the end of the season. All comparisons are made to control males or control females, and the relative differences in hormone concentrations between treatment and control birds, calculated separately for each sex, are presented for each time point. Males exposed to β-DBE-DBCH demonstrated significantly (p=0.05) lower concentrations of total thyroxine (TT 4 ) overall, that were 11-28% lower than those of control males at the individual sampling points, yet significantly higher (p=0.03) concentrations of free thyroxine (FT 4 ), that were 5-13% higher than those of control males at the individual sampling points; females had similar concentrations of TT 4 and FT 4 at the time of pairing, and T 4 was similar in both sexes at the end of the breeding season. Testosterone (T) concentrations in the treatment males were significantly higher during early (85%) and mid-courtship (30%) (time*treatment p=0.001), whereas females demonstrated a reduction in T at the time of pairing (17%, p=0.05). In the treatment females, concentrations of 17β-estradiol (E 2 ) showed a non-significant decrease (20%) and were positively correlated with T concentrations (p=0.03); E 2 concentrations were below quantification limits in males. For males, some variation in T was also significantly associated with their sexual behavior (p<0.001) and FT 4 concentrations (p=0.01). For females, there was no relationship between hormones measured at pairing and subsequent sexual behaviors or reproductive measures. This study demonstrates that exposure to β-DBE-DBCH at levels that are likely below those experienced by wild birds, affects the thyroid and sex steroid axes in birds and thus may be a contaminant of concern for wildlife warranting further research. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Thyroid function testing in elephant seals in health and disease.

PubMed

Yochem, Pamela K; Gulland, Frances M D; Stewart, Brent S; Haulena, Martin; Mazet, Jonna A K; Boyce, Walter M

2008-02-01

Northern Elephant Seal Skin Disease (NESSD) is a severe, ulcerative, skin condition of unknown cause affecting primarily yearling northern elephant seals (Mirounga angustirostris); it has been associated with decreased levels of circulating thyroxine (T4) and triiodothyronine (T3). Abnormalities of the thyroid gland that result in decreased hormone levels (hypothyroidism) can result in hair loss, scaling and secondary skin infections. However, concurrent illness (including skin ailments) can suppress basal levels of thyroid hormones and mimic hypothyroidism; when this occurs in animals with normal thyroid glands it is called "sick euthyroid syndrome". The two conditions (true hypothyroidism vs. "sick euthyroid") can be distinguished in dogs by testing the response of the thyroid gland to exogenous thyrotropin (Thyroid Stimulating Hormone, TSH). To determine whether hypothyroidism is involved in the etiology of NESSD, we tested thyroid function of stranded yearling elephant seals in the following categories: healthy seals (rehabilitated and ready for release; N=9), seals suffering from NESSD (N=16) and seals with other illnesses (e.g., lungworm pneumonia; N=10). Levels of T4 increased significantly for all three categories of elephant seals following TSH stimulation, suggesting that seals with NESSD are "sick euthyroid" and that the disease is not associated with abnormal thyroid gland function.

Evaluation of serum free thyroxine and thyrotropin concentrations in the diagnosis of canine hypothyroidism.

PubMed

Dixon, R M; Mooney, C T

1999-02-01

Canine thyroid-stimulating hormone (cTSH), total thyroxine (T4) and free T4 by equilibrium dialysis (fT4d) were measured in serum samples from 107 dogs with clinical signs suggestive of hypothyroidism in which the diagnosis was either confirmed (n = 30) or excluded (n = 77) by exogenous TSH response testing. Median serum total T4 and fT4d concentrations were significantly lower and cTSH significantly higher (P < 0.001) in hypothyroid compared with euthyroid dogs. Differential positive rate analysis determined optimal cut-off values of less than 14.9 nmol/litre (total T4), less than 5.42 pmol/litre (fT4d), greater than 0.68 ng/ml (cTSH), less than 17.3 (T4 to cTSH ratio), and less than 7.5 (fT4d to cTSH ratio) for hypothyroidism. These had a sensitivity and specificity of 100 and 75.3 per cent, 80 and 93.5 per cent, 86.7 and 81.8 per cent, 86.7 and 92.2 per cent, and 80 and 97.4 per cent, respectively, for diagnosing hypothyroidism. Corresponding areas under the receiver operating characteristic curves were 0.92, 0.93, 0.87, 0.93 and 0.93. Unexpectedly low cTSH values in hypothyroid dogs may have resulted from concurrent non-thyroidal illness. Unexpectedly high serum cTSH values in the euthyroid dogs might have resulted from recovery from illness or concurrent potentiated sulphonamide therapy. Measurement of endogenous cTSH concentration is a valuable diagnostic tool for canine hypothyroidism if used in association with assessment of T4. Estimation of fT4d added only limited additional information over total T4 measurement.

Relationship Between Changes in Serum Thyrotropin and Total and Lipoprotein Cholesterol with Prolonged Antarctic Residence

DTIC Science & Technology

1993-09-01

density lipoprotein ( HDL -C) cholesterol and triglyceride changes in TSH (P < .05)1 TBG (P < .01), TT3 (P < .05), ( TG ), on the other hand, were analyzed from...total thyroxine (TT4), free T4 (FT4), total T3 (TT3), free T3 (FT3), thyroid-binding globulin (TBG), total cholesterol (T-CHOL), high - density lipoprotein ... cholesterol ( HDL -C), triglyceride ( TG ), dietary cholesterol (D-CHOL), dietary fat (D-FAT), and dietary

Thyroxine-induced cardiac hypertrophy: influence of adrenergic nervous system versus renin-angiotensin system on myocyte remodeling.

PubMed

Hu, L W; Benvenuti, L A; Liberti, E A; Carneiro-Ramos, M S; Barreto-Chaves, M L M

2003-12-01

The present study assessed the possible involvement of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) in thyroxine (T4)-induced cardiac hypertrophy. Hemodynamic parameters, heart weight (HW), ratio of HW to body weight (HW/BW), and myocyte width were evaluated in absence of thyroid hormone (hypothyroidism) and after T4 administration. Male Wistar rats were used. Some were subjected to thyroidectomies, whereas hyperthyroidism was induced in others via daily intraperitoneal injection of T4 (25 or 100 microg x 100 g BW(-1) x day(-1)) for 7 days. In some cases, T4 administration was combined with the angiotensin I-converting enzyme inhibitor enalapril (Ena), with the angiotensin type 1 (AT1) receptor blocker losartan (Los) or with the beta-adrenergic blocker propanolol (Prop). Hemodynamics and morphology were then evaluated. Systolic blood pressure (SBP) was not altered by administration of either T4 alone or T4 in combination with the specific inhibitors. However, SBP decreased significantly in hypothyroid rats. An increased heart rate was seen after administration of either T4 alone or T4 in combination with either Los or Ena. Although the higher dose of T4 significantly increased HW, HW/BW increased in both T4-treated groups. Ena and Prop inhibited the increase in HW or HW/BW in hyperthyroid rats. Morphologically, both T4 dose levels significantly increased myocyte width, an occurrence prevented by RAS or SNS blockers. There was a good correlation between changes in HW/BW and myocyte width. These results indicate that T4-induced cardiac hypertrophy is associated with both the SNS and the RAS.

The effects of thyroxine or a GnRH analogue on thyroid hormone deiodination in the olfactory epithelium and retina of rainbow trout, Oncorhynchus mykiss, and sockeye salmon, Oncorhynchus nerka.

PubMed

Plate, E M; Adams, B A; Allison, W T; Martens, G; Hawryshyn, C W; Eales, J G

2002-06-01

Using low (0.5nM) substrate levels we determined the activities of thyroxine (T4) outer-ring deiodination (ORD), T4 inner-ring deiodination (T4IRD) and 3,5,3(')-triiodothyronine (T3) IRD activities in the olfactory epithelium (OLF) and retina (RET) of laboratory-held immature 1-year-old rainbow trout and immature 2.5-year-old sockeye salmon. In both species all three deiodination activities were detected in OLF and RET. For OLF, no particular pathway predominated and activities were similar to those of brain. For RET, T3IRD activity was greater than T4ORD activity and in sockeye RET T3IRD activity exceeded that of liver. Trout immersion for 6 weeks in 100ppm T4 increased plasma T4 levels 3-fold and plasma T3 levels by 50% and caused the anticipated autoregulatory responses in brain and liver deiodination ( downward arrow T4ORD, upward arrow T4IRD, and upward arrow T3IRD); OLF deiodination and RET T4ORD activity were unaltered but RET T4IRD and T3IRD activities increased dramatically. Two injections of a GnRH analogue (20 microgkg(-1)) into sockeye increased plasma T3 levels but not T4 levels and decreased RET T4IRD and T3IRD activities without changing liver, brain, or OLF deiodination. We conclude that in salmonids the main TH deiodination pathways occur in OLF but show no regulation by T4 or GnRH. In contrast, T3IRD activity predominates in RET and can be regulated by T4 and GnRH, suggesting that for RET plasma may be the major T3 source. These findings have implications for thyroidal regulation of sensory functions during salmonid diadromous migrations.

3,3'-Diiodothyronine sulfate excretion in maternal urine reflects fetal thyroid function in sheep.

PubMed

Wu, S Y; Huang, W S; Fisher, D A; Florsheim, W H; Kashiwai, K; Polk, D H

2001-09-01

We have shown that there is significant fetal-to-maternal transfer of sulfated metabolites of thyroid hormone after fetal infusion of a pharmacologic amount of 3,3',5-triiodothyronine (T(3)) or sulfated T(3) in late pregnancy in sheep (Am J Physiol 277:E915, 1999). The transferred iodothyronine sulfoconjugate, i.e. 3,3'-diiodothyronine sulfate (T(2)S), of fetal origin appears in maternal sheep urine. The present study was carried out to assess the contribution of T(2)S of fetal origin to the urinary pool in ewes. Eighteen date-bred ewes (mean gestational age of 115 d) and their twin fetuses were divided into four groups. In group I (control, n = 5), both ewes (M) and their fetuses (F) were sham operated for thyroidectomy (Tx). In group II, the ewes (MTx, n = 4) and, in group III, the fetuses (FTx, n = 4) were subjected to Tx. In group IV (MTx.FTx, n = 5), both the ewe and fetus had Tx. After 10-12 d, fetal and/or maternal hypothyroidism were confirmed by serum thyroxine (<15 nmol/L) measurements. In addition, we infused radioactive T(3) without disturbing the T(3) pool in three singleton near-term fetuses and assessed the amount of radioactive iodothyronine that appeared in maternal urine (MU). After infusing [(125)I-3'],3,5-T(3) via fetal vein to the near-term normal fetuses, radioactive T(2)S was identified as the major metabolite in MU by HPLC and T(2)S-specific antibody. MU T(2)S excretion (pmol/mmol creatinine) was significantly reduced by FTx and MTx.FTx but not by MTx. In addition, positive correlations (p < 0.01) were found between MU T(2)S excretion and fetal serum thyroxine and T(3) concentrations but not with maternal serum thyroxine or T(3) levels. T(2)S of fetal origin contributes significantly to the MU pool.

Thyroxine (T4) Test

MedlinePlus

... having too little thyroid hormone, a condition called hypothyroidism . Symptoms of hyperthyroidism, also known as overactive thyroid, ... Bulging of the eyes Trouble sleeping Symptoms of hypothyroidism, also known as underactive thyroid, include: Weight gain ...

A possible mechanism for the decrease in serum thyroxine level by phenobarbital in rodents

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

Kato, Yoshihisa, E-mail: kato@kph.bunri-u.ac.jp; Suzuki, Hiroshi; Haraguchi, Koichi

2010-12-15

Effects of phenobarbital (PB) on the levels of serum thyroid hormones such as total thyroxine (T{sub 4}) and triiodothyronine were examined in male mice, hamsters, rats, and guinea pigs. One day after the final administration of PB (80 mg/kg, intraperitoneal, once daily for 4 days), significant decreases in the levels of the serum total T{sub 4} and free T{sub 4} occurred in mice, hamsters, and rats, while a significant decrease in the level of serum triiodothyronine was observed in hamsters and rats among the animals examined. In addition, a significant decrease in the level of serum thyroid-stimulating hormone was observedmore » in only hamsters among the rodents examined. Significant increases in the level and activity of hepatic T{sub 4}-UDP-glucuronosyltransferase (UGT1A) after the PB administration occurred in mice, hamsters, and rats, while the increase in the amount of biliary [{sup 125}I]T{sub 4}-glucuronide after an intravenous injection of [{sup 125}I]T{sub 4} to the PB-pretreated animals occurred only in rats. In mice, rats, and hamsters, but not guinea pigs, PB pretreatment promoted the clearance of [{sup 125}I]T{sub 4} from the serum, led to a significant increase in the steady-state distribution volumes of [{sup 125}I]T{sub 4}, and raised the concentration ratio (Kp value) of the liver to serum and the liver distribution of [{sup 125}I]T{sub 4}. The present findings indicate that the PB-mediated decreases in the serum T{sub 4} level in mice, hamsters, and rats, but not guinea pigs, occur mainly through an increase in the accumulation level of T{sub 4} in the liver.« less

Utilizing mass spectrometry imaging to map the thyroid hormones triiodothyronine and thyroxine in Xenopus tropicalis tadpoles.

PubMed

Goto-Inoue, Naoko; Sato, Tomohiko; Morisasa, Mizuki; Kashiwagi, Akihiko; Kashiwagi, Keiko; Sugiura, Yuki; Sugiyama, Eiji; Suematsu, Makoto; Mori, Tsukasa

2018-02-01

Thyroid hormones are not only responsible for thermogenesis and energy metabolism in animals, but also have an important role in cell differentiation and development. Amphibian metamorphosis provides an excellent model for studying the remodeling of the body. This metamorphic organ remodeling is induced by thyroid hormones, and a larval body is thus converted into an adult one. The matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry (MS) imaging technology is expected to be a suitable tool for investigating small bioreactive molecules. The present study describes the distribution of the thyroid hormones, i.e., triiodothyronine (T3) and thyroxine (T4) and their inactive form reverse T3 (rT3) in Xenopus tropicalis tadpoles using two different types of imaging techniques, MS/MS and Fourier transform (FT)-MS imaging. As a result of MS/MS imaging, we demonstrated that T3 was mainly distributed in the gills. T4 was faintly localized in the eyes, inner gills, and intestine during metamorphosis. The intensity of T3 in the gills and the intensity of T4 in the body fluids were increased during metamorphosis. Moreover, the localization of the inactive form rT3 was demonstrated to be separate from T3, namely in the intestine and muscles. In addition, FT-MS imaging could utilize simultaneous imaging including thyroid hormone. This is the first report to demonstrate the molecular distribution of thyroid hormones themselves and to discriminate T3, T4, and rT3 in animal tissues.

Thyroid hormones and deiodinase activity in plasma and tissues in relation to high levels of organohalogen contaminants in East Greenland polar bears (Ursus maritimus).

PubMed

Gabrielsen, Kristin Møller; Krokstad, Julie Stene; Villanger, Gro Dehli; Blair, David A D; Obregon, Maria-Jesus; Sonne, Christian; Dietz, Rune; Letcher, Robert J; Jenssen, Bjørn Munro

2015-01-01

Previous studies have shown relationships between organohalogen contaminants (OHCs) and circulating levels of thyroid hormones (THs) in arctic wildlife. However, there is a lack of knowledge concerning the possible functional effects of OHCs on TH status in target tissues for TH-dependent activity. The relationships between circulating (plasma) levels of OHCs and various TH variables in plasma as well as in liver, muscle and kidney tissues from East Greenland sub-adult polar bears (Ursus maritimus) sampled in 2011 (n=7) were therefore investigated. The TH variables included 3.3',5.5'-tetraiodothyronine or thyroxine (T4), 3.3',5-triiodothyronine (T3) and type 1 (D1) and type 2 (D2) deiodinase activities. Principal component analysis (PCA) combined with correlation analyses demonstrated negative relationships between individual polychlorinated biphenyls (PCBs) and their hydroxylated (OH-) metabolites and T4 in both plasma and muscle. There were both positive and negative relationships between individual OHCs and D1 and D2 activities in muscle, liver and kidney tissues. In general, PCBs, OH-PCBs and polybrominated dipehenyl ethers (PBDEs) were positively correlated to D1 and D2 activities, whereas organochlorine pesticides and byproducts (OCPs) were negatively associated with D1 and D2 activities. These results support the hypothesis that OHCs can affect TH status and action in the target tissues of polar bears. TH levels and deiodinase activities in target tissues can be sensitive endpoints for exposure of TH-disrupting compounds in arctic wildlife, and thus, tissue-specific responses in target organs should be further considered when assessing TH disruption in wildlife studies. Copyright © 2014 Elsevier Inc. All rights reserved.

Validation of a novel high-sensitivity radioimmunoassay procedure for measurement of total thyroxine concentration in psittacine birds and snakes.

PubMed

Greenacre, C B; Young, D W; Behrend, E N; Wilson, G H

2001-11-01

To validate a novel high-sensitivity radioimmunoassay (RIA) procedure developed to accurately measure the relatively low serum total thyroxine (T4) concentrations of birds and reptiles and to establish initial reference ranges forT4 concentration in selected species of psittacine birds and snakes. 56 healthy nonmolting adult psittacine birds representing 6 species and 42 captive snakes representing 4 species. A solid-phase RIA designed to measure free T4 concentrations in dialysates of human serum samples was used without dialysis to evaluate total T4 concentration in treated samples obtained from birds and reptiles. Serum T4 binding components were removed to allow assay of undialyzed samples. Assay validation was assessed by determining recovery of expected amounts of T4 in treated samples that were serially diluted or to which T4 was added. Intra- and interassay coefficient of variation (CV) was determined. Mean recovery of T4 added at 4 concentrations ranged from 84.9 to 115.0% and 95.8 to 119.4% in snakes and birds, respectively. Intra- and interassay CV was 3.8 and 11.3%, respectively. Serum total T4 concentrations for 5 species of birds ranged from 2.02 to 768 nmol/L but ranged from 3.17 to 142 nmol/L for blue-fronted Amazon parrots; concentrations ranged from 0.21 to 6.06 nmol/L for the 4 species of snakes. This new RIA method provides a commercially available, accurate, and sensitive method for measurement of the relatively low serum T4 concentrations of birds and snakes. Initial ranges for the species evaluated were established.

Local renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy.

PubMed

Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

1999-01-01

We have reported previously that thyroid hormone activates the circulating and tissue renin-angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin-angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin-angiotensin system in Sprague-Dawley rats was fixed by chronic angiotensin II infusion (40 ng/min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0.1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0.12+/-0.03 and 0.15+/-0.03 microgram/h per liter, 126+/-5 and 130+/-5 ng/l respectively) (means+/-s.e.m.). Despite stabilization of the circulating renin-angiotensin system, thyroid hormone induced cardiac hypertrophy (5.0+/-0.5 vs 3.5+/-0.1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74+/-2 vs 48+/-2%, 6.5+/-0.8 vs 3.8+/-0.4 ng/h per g, 231+/-30 vs 149+/-2 pg/g respectively). These results indicate that the local renin-angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy.

Pineal-Induced Depression of Free Thyroxine in Syrian Hamsters

DTIC Science & Technology

1985-01-01

activation by blind- ness in Syrian hamsters, can influence free 14 concentration. MATERIALS AND METHODS Male golden hamsters, Mesocricetus auratus...considered that the changes in T4 passively result from pineal- induced hypogonadism and the possible resultant effects on T4 serum bind- ing proteins...the presence of pineal-induced hypogonadism and that, like T4 and FT41, -• ’. 328 Vaughan and Pruitt TESrE S PROSTATE 0.6 80- 20 gn Mgm ,... =_ 9 Mg_

Effects of triiodothyronine on turnover rate and metabolizing enzymes for thyroxine in thyroidectomized rats.

PubMed

Nagao, Hidenori; Sasaki, Makoto; Imazu, Tetsuya; Takahashi, Kenjo; Aoki, Hironori; Minato, Kouichi

2014-10-29

Previous studies in rats have indicated that surgical thyroidectomy represses turnover of serum thyroxine (T4). However, the mechanism of this process has not been identified. To clarify the mechanism, we studied adaptive variation of metabolic enzymes involved in T4 turnover. We compared serum T4 turnover rates in thyroidectomized (Tx) rats with or without infusion of active thyroid hormone, triiodothyronine (T3). Furthermore, the levels of mRNA expression and activity of the metabolizing enzymes, deiodinase type 1 (D1), type 2 (D2), uridine diphosphate-glucuronosyltransferase (UGT), and sulfotransferase were also compared in several tissues with or without T3 infusion. After the T3 infusion, the turnover rate of serum T4 in Tx rats returned to normal. Although mRNA expression and activity of D1 decreased significantly in both liver and kidneys without T3 infusion, D2 expression and activity increased markedly in the brain, brown adipose tissue, and skeletal muscle. Surprisingly, hepatic UGT mRNA expression and activity in Tx rats increased significantly in comparison with normal rats, and returned to normal after T3 infusion. This study suggests that repression of the disappearance of serum T4 in rats after Tx is a homeostatic response to decreased serum T3 concentrations. Additionally, T4 glucuronide is a storage form of T4, but may also have biological significance. These results suggest strongly that repression of deiodination of T4 by D1 in the liver and kidneys plays a major role in thyroid hormone homeostasis in Tx rats, and that hepatic UGT also plays a key role in this mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

Childhood thyromegaly: recent developments

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

Reiter, E.O.; Root, A.W.; Rettig, K.

1981-10-01

Evaluation of a child with goiter includes historical review, physical examination, and measurement of serum concentrations of PBI, T4 and T3RU, TSH, and titers of antithyroglobulin and antithyroid microsomal antibodies. If there are no indications for more intensive evaluation such as history of cervical irradiation, a palpable abnormality of the thyroid gland or unusual laboratory findings (e.g., a significant PBI-thyroxine iodine discrepancy in the absence of a positive antithyroid antibody titer), a trial of TSH-suppressive therapy with thyroxine is undertake, even if the cause of thyromegaly has not been identified. If thyroid size diminishes in the ensuing six to 12more » months, treatment is maintained for approximately two years and then discontinued. If the goiter recurs, or if there is impaired thyroid function, treatment is resumed. Periodically, antithyroid antibody titers and indices of thyroid function are determined. If the goiter does not diminish after a reasonable trial of suppressive therapy with adequate amounts of thyroxine (i.e., those quantities which will inhibit TRH-induced secretion of TSH), subtotal thyroidectomy is recommended to be certain that an underlying neoplasm has not been overlooked. A biopsy of the thyroid is not performed routinely in such children prior to operative therapy. Almost invariably, examination of the surgical specimen reveals CLT. Postoperatively, suppressive doses of thyroxine are maintained indefinitely. Inasmuch as thyroxine suppression of TSH secretion is essential in the management of patients with thyroid neoplasms, a limited medical trial, as described, does not place the patient at undue risk.« less

Plasma thyroxine changes of the Apollo crewmen

NASA Technical Reports Server (NTRS)

Sheinfeld, M.; Leach, C. S.; Johnson, P. C.

1975-01-01

Blood drawn from Apollo crew members prior to the mission, at recovery, and postmission, was used to examine the effect Apollo mission activities have on thyroid hormone levels. At recovery, statistically significant increases in thyroxine and the free thyroxine index were found. Serum cholesterol and triglycerides were decreased. No change of statistical significance was found in the T3 binding percentage, total serum proteins, and albumin. We conclude that Apollo activities and environment caused the postmission increase in plasma thyroxine. The prolonged postmission decreases in serum cholesterol may be one result of the increased thyroxine activity.

Total and free thyroxine and triiodothyronine: measurement discrepancies, particularly in inpatients.

PubMed

Jonklaas, Jacqueline; Sathasivam, Anpalakan; Wang, Hong; Gu, Jianghong; Burman, Kenneth D; Soldin, Steven J

2014-09-01

We compared the performance of tandem mass spectrometry versus immunoassay for measuring thyroid hormones in a diverse group of inpatients and outpatients. Thyroxine (T4), triiodothyronine (T3), free thyroxine (FT4), and free triiodothyronine (FT3) were measured by liquid chromatography tandem mass spectrometry and immunoassay in 100 patients and the two assays were compared. T4 and T3 values measured by the two different assays correlated well with each other (r=0.91-0.95). However, the correlation was less good at the extremes (r=0.51-0.75). FT4 and FT3 concentrations measured by the two assays correlated less well with each other (r=0.75 and 0.50 respectively). The studied analytes had poor inverse correlation with the log-transformed TSH values (r=-0.22-0.51) in the population as a whole. The strongest correlations were seen in the groups of outpatients (r=-0.25-0.61). The weakest degree of correlation was noted in the inpatient group, with many correlations actually being positive. The worst between-assay correlation was demonstrated at low and high hormone concentrations, in the very concentration ranges where accurate assay performance is typically most clinically important. Based on the lesser susceptibility of mass spectrometry to interferences from conditions such as binding protein abnormalities, we speculate that mass spectrometry better reflects the clinical situation. In this mixed population of inpatients and outpatients, we also note failure of assays to conform to the anticipated inverse linear relationship between thyroid hormones and log-transformed TSH. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Serum heart type fatty acid binding protein levels are not changed in hyperthyroidism.

PubMed

Ozbek, Mustafa; Gungunes, Askin; Sahin, Mustafa; Ginis, Zeynep; Ucan, Bekir; Sayki, Muyesser; Tutal, Esra; Cakal, Erman; Kuşkonmaz, Serife M; Öztürk, Mehmet A; Delibasi, Tuncay

2016-09-01

Heart type fatty acid binding protein (H-FABP) is a small protein and released into the circulation when myocardial damage has occurred. Previous studies have demonstrated that H-FABP is closely associated with cardiac and some endocrinologic disorders including prediabetes, metabolic syndrome, and acromegaly. Hyperthyroism is a well-known disorder associated with cardiovascular diseases. We aimed to investigate the effect of hyperthyrodism on H-FABP levels. Forty six patients with hyperthyroidism with no known history of coronary artery disease and 40 healthy controls are involved in the study. Serum H-FABP levels are measured using sandwich enzyme-linked immunosorbent assay. There was no significant difference between serum H-FABP levels of patients with hyperthyroidism and controls (871±66 pg/mL, and 816±66 pg/mL, respectively P=0.56). There was no significant correlation between H-FABP, free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels in patients and controls. Serum H-FABP levels are not altered in patients with hyperthyroidism.

THE PENALIZED OPTIMAL EXPERIMENTAL DESIGN: THE PRECISE ESTIMATION OF AN INTERACTION THRESHOLD IN A MIXTURE OF EIGHTEEN POLYHALOGENATED AROMATIC HYDROCARBONS.

EPA Science Inventory

Crofton et al. (EHP, 2005) conducted a study of 18 polyhalogenated aromatic hydrocarbons (PHAHs) on serum total thyroxine (T4). Young female Long-Evans rats were dosed with the 18 single agents or a fixed-ratio mixture, and serum total T4 was measured via radioimmunoassay. The i...

The effect of Brazilian propolis on serum thyroid hormones in broilers reared under chronic heat stress

USDA-ARS?s Scientific Manuscript database

This experiment evaluated the effect of dietary supplement with green Brazilian propolis on serum thyroxin (T4) and tri-iodothyronine (T3) levels in broiler chickens exposed to chronic heat stress for 4 wks (from 15 to 42 d of age). Five hundred and four 15-d-old, male broiler chickens (Ross 708) w...

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-01-01

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

Purification and characterization of rat liver nuclear thyroid hormone receptors.

PubMed Central

Ichikawa, K; DeGroot, L J

1987-01-01

Nuclear thyroid hormone receptor was purified to 904 pmol of L-3,5,3'-triiodothyronine (T3) binding capacity per mg of protein with 2.5-5.2% recovery by sequentially using hydroxylapatite column chromatography, ammonium sulfate precipitation, Sephadex G-150 gel filtration, DNA-cellulose column chromatography, DEAE-Sephadex column chromatography, and heparin-Sepharose column chromatography. Assuming that one T3 molecule binds to the 49,000-Da unit of the receptor, we reproducibly obtained 6.4-14.7 micrograms of receptor protein with 4.2-4.9% purity from 4-5 kg of rat liver. Elution of receptor from the heparin-Sepharose column was performed using 10 mM pyridoxal 5'-phosphate, which was observed to diminish binding of receptor to heparin-Sepharose or DNA-cellulose. This effect was specific for pyridoxal 5'-phosphate, since related compounds were not effective. Purified receptor bound T3 with high affinity (6.0 X 10(9) liter/mol), and the order of affinity of iodothyronine analogues to purified receptor was identical to that observed with crude receptor preparations [3,5,3'-triiodothyroacetic acid greater than L-T3 greater than D-3,5,3'-triiodothyronine (D-T3) greater than L-thyroxine greater than D-thyroxine]. Purified receptor had a sedimentation coefficient of 3.4 S, Stokes radius of 34 A, and calculated molecular mass of 49,000. Among several bands identified by silver staining after electrophoresis in NaDodSO4/polyacrylamide gels, one 49,000-Da protein showed photoaffinity labeling with [125I]thyroxine that was displaceable with excess unlabeled T3. The tryptic fragment and endogenous proteinase-digested fragment of the affinity-labeled receptor showed saturable binding in 27,000-Da and 36,000-Da peptides, respectively. These molecular masses are in agreement with estimates from gel filtration and gradient sedimentation, indicating that affinity labeling occurred at the hormone binding domain of nuclear thyroid hormone receptor. This procedure reproducibly provides classical native rat liver T3 nuclear receptor in useful quantity and purity and of the highest specific activity so far reported. Images PMID:3472213

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

PubMed

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

2017-05-01

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

Do Thyroxine and Thyroid-Stimulating Hormone Levels Reflect Urinary Iodine Concentrations?

PubMed Central

Soldin, Offie P.; Tractenberg, Rochelle E.; Pezzullo, John C.

2013-01-01

The toxicity of environmental chemicals such as nitrates, thiocynates, and perchlorates, some therapeutics, and dietary goitrogens can lower thyroidal iodine uptake and result in hypothyroidism and goiter. Iodine sufficiency, essential for normal thyroid hormone synthesis, is critical during gestation to assure that sufficient thyroxine (T4) and iodine reach the developing fetus. Spot urinary iodide (UI) measurements are used globally to indicate and monitor iodine sufficiency of populations. In individuals, however, UI are not routinely measured; instead, normal serum thyroid-stimulating hormone (TSH) and T4 concentrations serve as surrogate indicators of iodine sufficiency as well as thyroidal health. Our objective was to examine the relationship between UI concentrations and serum T4 and TSH concentrations in individuals in an ‘‘iodine-sufficient population.’’ Using a cross-sectional sample of the US population (n = 7628) from the National Health and Nutrition Examination Survey (NHANES III; 1988–1994) database, we examined the relationship among UI, T4, and TSH in pregnant and nonpregnant women and in men (15–44 years). There was a lack of relationship between UI (or UI/Cr) concentrations and serum T4 or TSH concentrations. Therefore, TSH and T4 are not appropriate markers of UI concentrations in this population. Monitoring the status of iodine nutrition of individuals in the United States may be important because serum TSH and T4 concentrations do not indicate low iodine status. PMID:15795649

Corticosterone and thyroxine in cold-stunned Kemp's ridley sea turtles (Lepidochelys kempii).

PubMed

Hunt, Kathleen E; Innis, Charles; Rolland, Rosalind M

2012-09-01

Kemp's ridley sea turtles (Lepidochelys kempii), a critically endangered species, frequently strand on the shores of Cape Cod (Massachusetts, USA) in late autumn in a state of "cold-stunning" exhibiting low body temperature and related clinical issues. Stranded turtles are transported to the New England Aquarium (Boston, Massachusetts, USA) for treatment and rehabilitation. This study tested the hypothesis that cold-stunned sea turtles might exhibit high corticosterone ("stress hormone") or low thyroxine (which is often affected by temperature), or both, and that monitoring of both hormones may be useful for assessing recovery. In a retrospective analysis, 87 archived plasma samples were assayed from 56 cold-stunned juvenile Kemp's ridley sea turtles for corticosterone and free thyroxine (fT4). Upon admission, mean corticosterone was the highest yet reported for a population of sea turtles (39.3 +/- 2.5 ng/ml; mean +/- standard error of the mean [SEM]) and fT4 was usually undetectable. On admission, corticosterone was negatively correlated with white blood cell count but was not correlated with blood glucose. There were no differences in either hormone between survivors and nonsurvivors on admission. After 18+ days in recovery, surviving turtles' corticosterone dropped significantly to levels typical of baseline in other species (0.9 +/- 1.0 ng/ml) while fT4 increased significantly (1.3 +/- 1.5 pg/ml). During recovery, corticosterone was positively correlated with blood glucose and was not correlated with white blood cell count. Turtles that showed persistent deficits in feeding, activity, or both during recovery had significantly lower fT4 than did turtles with no such deficits. The "high corticosterone, low fT4" endocrine profile seen on admission may be a useful marker of cold-stunning in this and other species. Further studies are necessary to determine whether low thyroid hormones play a causal role in deficits in feeding and activity during recovery. Monitoring of both hormones may be useful for triage, monitoring of recovery, and assessing readiness for release.

Prolonged weightlessness effect on postflight plasma thyroid hormones

NASA Technical Reports Server (NTRS)

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

1977-01-01

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

Serum transthyretin concentration is decreased in dogs with nonthyroidal illness.

PubMed

Piechotta, Marion; Jens, Raila; Rick, Markus; Beyerbach, Martin; Hoppen, Hans-Otto

2012-03-01

Hypothyroidism in dogs is often difficult to diagnose owing to nonspecific clinical signs and laboratory test results that can be mimicked by nonthyroidal illness (NTI). Thyroxine (T4) circulates in blood mainly bound to T4-binding globulin and, to a lesser degree, transthyretin (TTR) and albumin. The concentration of total T4 depends on the concentrations of these binding proteins. We hypothesized that dogs with NTI and decreased serum total T4 concentrations would have decreased serum TTR concentrations. The objective of the study was to measure and compare serum TTR concentrations in healthy dogs, in dogs with NTI and low serum T4 concentrations, and in dogs with hypothyroidism. Assignment of dogs to 3 groups was based on physical examination and serum concentrations of T4 and TSH (mean ± SD): for healthy dogs (n = 13), T4 was 24.8 ± 3.6 nmol/L and TSH was 0.15 ± 0.08 μg/L; for dogs with NTI and low T4 (n = 20), T4 was 3.2 ± 3.0 nmol/L and TSH was 0.18 ± 0.13 μg/L; and for hypothyroid dogs (n = 19), T4 was 5.3 ± 4.3 nmol/L and TSH was 2.33 ± 1.90 μg/L). TTR concentrations in serum were determined semiquantitatively using western blot analysis. Serum TTR concentration (mean ± SD) was decreased in the dogs with NTI (24.8 ± 7.9 mg/L) compared with that of hypothyroid dogs (41.1 ± 21.4 mg/L, P = .0035). Differences were not found between TTR concentrations in clinically healthy dogs (33.3 ± 10.1 mg/L) and hypothyroid dogs or dogs with NTI. Serum TTR concentrations were significantly decreased in dogs with NTI and low T4 compared with concentrations in hypothyroid dogs. Additional studies should be done to determine if TTR concentrations can discriminate between dogs with NTI and low T4 and dogs with primary hypothyroidism. © 2012 American Society for Veterinary Clinical Pathology.

Laparoscopic sleeve gastrectomy leads to reduction in thyroxine requirement in morbidly obese patients with hypothyroidism.

PubMed

Aggarwal, Sandeep; Modi, Shrey; Jose, Toney

2014-10-01

The impact of laparoscopic sleeve gastrectomy (LSG) on various co-morbidities including type II diabetes mellitus, hypertension, and sleep apnea is well established. However, its effect on hypothyroidism has not been given due attention evidenced by the scant literature on the subject. The purpose of this report is to assess the change in thyroxine (T4) requirement in morbidly obese patients with clinical hypothyroidism after LSG. We conducted a retrospective review of morbidly obese patients on T4 replacement therapy for clinical hypothyroidism who underwent LSG from August 2009 to July 2012 at our institution. Of the 200 patients who underwent LSG during this period, 21 (10.5 %) were on T4 replacement therapy preoperatively for clinical hypothyroidism. Two patients were lost to follow-up. The remaining 19 patients were categorized into two groups. Group 1 comprised 13 patients with decreased T4 requirements after LSG. Group 2 comprised six patients in whom the T4 dose remained unaltered. The mean change in T4 requirement in group 1 was 42.07 % (12-100 %). Group 1 patients had a significantly higher mean preoperative body mass index (48.7 vs. 43.0 kg/m(2); p = 0.03) than the group 2 patients. There was a significant correlation between the percentage excess weight loss and the percentage change in T4 requirement in group 1 (r = 0.607, p = 0.028). Sleeve gastrectomy has a favorable impact on hypothyroid status as seen by a reduction in T4 requirement in the majority of morbidly obese patients with overt hypothyroidism.

Thyroid hormone determines the start of the sensitive period of imprinting and primes later learning.

PubMed

Yamaguchi, Shinji; Aoki, Naoya; Kitajima, Takaaki; Iikubo, Eiji; Katagiri, Sachiko; Matsushima, Toshiya; Homma, Koichi J

2012-01-01

Filial imprinting in precocial birds is the process of forming a social attachment during a sensitive or critical period, restricted to the first few days after hatching. Imprinting is considered to be part of early learning to aid the survival of juveniles by securing maternal care. Here we show that the thyroid hormone 3,5,3'-triiodothyronine (T(3)) determines the start of the sensitive period. Imprinting training in chicks causes rapid inflow of T(3), converted from circulating plasma thyroxine by Dio2, type 2 iodothyronine deiodinase, in brain vascular endothelial cells. The T(3) thus initiates and extends the sensitive period to last more than 1 week via non-genomic mechanisms and primes subsequent learning. Even in non-imprinted chicks whose sensitive period has ended, exogenous T(3) enables imprinting. Our findings indicate that T(3) determines the start of the sensitive period for imprinting and has a critical role in later learning.

Thyroid hormone determines the start of the sensitive period of imprinting and primes later learning

PubMed Central

Yamaguchi, Shinji; Aoki, Naoya; Kitajima, Takaaki; Iikubo, Eiji; Katagiri, Sachiko; Matsushima, Toshiya; Homma, Koichi J.

2012-01-01

Filial imprinting in precocial birds is the process of forming a social attachment during a sensitive or critical period, restricted to the first few days after hatching. Imprinting is considered to be part of early learning to aid the survival of juveniles by securing maternal care. Here we show that the thyroid hormone 3,5,3′-triiodothyronine (T3) determines the start of the sensitive period. Imprinting training in chicks causes rapid inflow of T3, converted from circulating plasma thyroxine by Dio2, type 2 iodothyronine deiodinase, in brain vascular endothelial cells. The T3 thus initiates and extends the sensitive period to last more than 1 week via non-genomic mechanisms and primes subsequent learning. Even in non-imprinted chicks whose sensitive period has ended, exogenous T3 enables imprinting. Our findings indicate that T3 determines the start of the sensitive period for imprinting and has a critical role in later learning. PMID:23011135

Evaluation of two over-the-counter natural thyroid hormone preparations in human volunteers.

PubMed

Csako, G; Corso, D M; Kestner, J; Bokser, A D; Kennedy, P E; Pucino, F

1992-04-01

To determine the pharmacologic activity of over-the-counter (OTC) thyroid preparations. In vitro analysis and a prospective, crossover study in vivo. Tertiary care center. Two healthy adult volunteers. Three OTC preparations (Thyrotrophin PMG [bovine thyroid PMG extract], Thyro Forte [thyroid lymphogland concentrate with synergistic complex], and Thyro Complex [thyroid lyophilized gland concentrate with synergistic complex]) were analyzed in vitro. Volunteers were administered two times the manufacturer's maximum recommended daily dose of either Thyrotrophin PMG or Thyro Forte for one week, washed out for four to five weeks, and crossed over to receive the opposite tablet preparation for an additional week. The triiodothyronine (T3) and thyroxine (T4) contents of OTC preparations were measured by HPLC. Vital signs, serum total and free T4, total T3, thyroid stimulating hormone, thyroxine binding globulin, thyroglobulin, and general chemistry tests (including glucose and cholesterol) were monitored before, during, and between administration of the products. HPLC analysis of the three OTC preparations showed no T4 but did show possible T3 in two of these products. We found no definite clinical or laboratory evidence of thyroid hormone excess with either product. Healthcare professionals should advise against the use of these scientifically unsound and relatively expensive OTC thyroid preparations, of which the therapeutic efficacy is unknown.

Cavity filling mutations at the thyroxine-binding site dramatically increase transthyretin stability and prevent its aggregation.

PubMed

Sant'Anna, Ricardo; Almeida, Maria Rosário; Varejāo, Nathalia; Gallego, Pablo; Esperante, Sebastian; Ferreira, Priscila; Pereira-Henriques, Alda; Palhano, Fernando L; de Carvalho, Mamede; Foguel, Debora; Reverter, David; Saraiva, Maria João; Ventura, Salvador

2017-03-24

More than a hundred different Transthyretin (TTR) mutations are associated with fatal systemic amyloidoses. They destabilize the protein tetrameric structure and promote the extracellular deposition of TTR as pathological amyloid fibrils. So far, only mutations R104H and T119M have been shown to stabilize significantly TTR, acting as disease suppressors. We describe a novel A108V non-pathogenic mutation found in a Portuguese subject. This variant is more stable than wild type TTR both in vitro and in human plasma, a feature that prevents its aggregation. The crystal structure of A108V reveals that this stabilization comes from novel intra and inter subunit contacts involving the thyroxine (T 4 ) binding site. Exploiting this observation, we engineered a A108I mutation that fills the T 4 binding cavity, as evidenced in the crystal structure. This synthetic protein becomes one of the most stable TTR variants described so far, with potential application in gene and protein replacement therapies.

Blood-based biomarkers of selenium and thyroid status indicate possible adverse biological effects of mercury and polychlorinated biphenyls in Southern Beaufort Sea polar bears.

PubMed

Knott, Katrina K; Schenk, Patricia; Beyerlein, Susan; Boyd, Daryle; Ylitalo, Gina M; O'Hara, Todd M

2011-11-01

We examined biomarkers of selenium status (whole blood Se; serum Se; glutathione peroxidase activity) and thyroid status (concentrations and ratios of thyroxine, T4; tri-iodothyronine, T3; albumin) in polar bears to assess variations among cohorts, and relationships to circulating concentrations of contaminants. Concentrations of total mercury (Hg) in whole blood were similar among cohorts (prime aged males and females, older animals, ages≥16 years, and young animals, ages 1-5 years; 48.44±35. 81; p=0.253). Concentrations of sum of seven polychlorinated biphenyls (∑PCB7) in whole blood were greater in females (with and without cubs, 26.44±25.82 ng/g ww) and young (26.81±10.67 ng/g ww) compared to males (8.88±5.76 ng/g ww, p<0.001), and significantly related to reduced body condition scores (p<0.001). Concentrations of Se and albumin were significantly greater in males than females (whole blood Se, males, 42.34 pmol/g ww, females, 36.25±6.27 pmol/g ww, p=0.019; albumin, males, 4.34±0.34 g/dl, females, 4.10±0.29 g/dL, p=0.018). Glutathione peroxidase activity ranged from 109.1 to 207.8 mU/mg hemoglobin, but did not differ significantly by sex or age (p>0.08). Thyroid hormones were greater in females (solitary females and females with cubs) compared to males (p<0.001). Biomarkers of Se status and concentrations of T3 were significantly positively related to Hg in all prime aged polar bears (p<0.03). Albumin concentrations were significantly positively related to total TT4, and significantly negatively related to concentrations of ∑PCB7 (p<0.003). Total thyroxine (TT4) was significantly negatively associated with blood concentrations of ∑PCB7 in solitary females (p=0.045). These data suggest that female polar bears were more susceptible to changes in blood-based biomarkers of selenium and thyroid status than males. Further classifications of the physiologic states of polar bears and repeated measures of individuals over time are needed to accurately assess the biological impact of combined toxicant exposures. Copyright © 2011 Elsevier Inc. All rights reserved.

Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency

PubMed Central

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

2015-01-01

Several influences modulate biochemical responses to a weight-adjusted levothyroxine (l-T4) replacement dose. We conducted a secondary analysis of the relationship of l-T4 dose to TSH and free T3 (FT3), using a prospective observational study examining the interacting equilibria between thyroid parameters. We studied 353 patients on steady-state l-T4 replacement for autoimmune thyroiditis or after surgery for malignant or benign thyroid disease. Peripheral deiodinase activity was calculated as a measure of T4–T3 conversion efficiency. In euthyroid subjects, the median l-T4 dose was 1.3 μg/kg per day (interquartile range (IQR) 0.94,1.60). The dose was independently associated with gender, age, aetiology and deiodinase activity (all P<0.001). Comparable FT3 levels required higher l-T4 doses in the carcinoma group (n=143), even after adjusting for different TSH levels. Euthyroid athyreotic thyroid carcinoma patients (n=50) received 1.57 μg/kg per day l-T4 (IQR 1.40, 1.69), compared to 1.19 μg/kg per day (0.85,1.47) in autoimmune thyroiditis (P<0.01, n=76) and 1.08 μg/kg per day (0.82, 1.44) in patients operated on for benign disease (P< 0.01, n=80). Stratifying patients by deiodinase activity categories of <23, 23–29 and >29 nmol/s revealed an increasing FT3–FT4 dissociation; the poorest converters showed the lowest FT3 levels in spite of the highest dose and circulating FT4 (P<0.001). An l-T4-related FT3–TSH disjoint was also apparent; some patients with fully suppressed TSH failed to raise FT3 above the median level. These findings imply that thyroid hormone conversion efficiency is an important modulator of the biochemical response to l-T4; FT3 measurement may be an additional treatment target; and l-T4 dose escalation may have limited success to raise FT3 appropriately in some cases. PMID:26335522

Thyroid and Biochemical/Metabolic Effects of PFDA (Perfluoro-n-decanoic Acid).

DTIC Science & Technology

1988-01-04

could be explained by a chemically induced hypothyroidism. Experiments employing T4- supplementation suggests that the toxicity is more complex. Rats... supplementation was continued through the day prior to sacrifice. The liver enzymes c-glycerolphosphate dehydro- genase (GPD) and malic enzyme (ME) were...T4 supplementation had differential effects on anorexia, body wasting and hypothermia. Thyroxine supplementation completely prevented the PFDA-induced

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

EPA Science Inventory

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

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

EPA Science Inventory

The present study investigated whether inhibition of deiodinase, the enzyme which converts thyroxine (T4) to the more biologically-active form, 3,5,3'-triiodothyronine (T3), would impact inflation of the posterior and/or anterior chamber of the swim bladder, processes previously ...

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

EPA Science Inventory

The present study investigated whether inhibition of deiodinase, the enzyme which converts thyroxine (T4) to the more biologically-active form, 3,5,3'-triiodothyronine (T3), would impact inflation of the posterior and/or anterior chamber of the swim bladder, processes previously ...

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

EPA Science Inventory

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

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

PubMed Central

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

2005-01-01

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

Thyroxine treatment may be useful for subclinical hypothyroidism in patients with female infertility.

PubMed

Yoshioka, Waka; Amino, Nobuyuki; Ide, Akane; Kang, Shino; Kudo, Takumi; Nishihara, Eijun; Ito, Mitsuru; Nakamura, Hirotoshi; Miyauchi, Akira

2015-01-01

Infertile women sometimes associated with subclinical hypothyroidism (SCH). The guidelines of the American Endocrine Society, and American Association of Clinical Endocrinologists and American Thyroid Association recommend treatment with thyroxine (T4) for patients with SCH who want to have children. We examined 69 female infertile patients with SCH and the effects of levothyroxine (l-T4) therapy on pregnancy rates and pregnancy outcomes were observed. Fifty-eight (84.1%) patients successfully conceived during the T4 treatment period (Group A), although 17 patients (29.3%) had miscarriage afterward. The remaining 11 patients continued to be infertile (Group B). The median TSH value in Group A before the T4 treatment was 5.46 μIU/mL (range 3.1-13.3) and this significantly decreased to 1.25 μIU/mL (range 0.02-3.75) during the treatment (p<0.001). The estimated duration of infertility before the T4 treatment was 2.8±1.7 years and the duration until pregnancy after the treatment was significantly shorter at 0.9±0.9 years (p<0.001). Shortening of the infertile period after the T4 therapy was observed not only in patients who were treated with assisted reproductive technology (ART) but also in patients who conceived spontaneously in Group A. Administered T4 dose was 54.3±14.2 μg before pregnancy and 68.5±22.8 μg during pregnancy (p<0.001). Anti-thyroid autoantibodies were identified in 42.0% of all patients and no significant difference was observed in positivity between Group A and Group B. High successful pregnancy rate and shorter duration of infertility until pregnancy after T4 treatment strongly suggest that T4 enhanced fertility in infertile patients with SCH.

Exacerbation of underlying hypothyroidism caused by proteinuria and induction of urinary thyroxine loss: case report and subsequent investigation.

PubMed

Chandurkar, Vikram; Shik, John; Randell, Edward

2008-01-01

To describe a patient with excess urinary thyroxine (T4) excretion and worsening of preexisting hypothyroidism in the setting of nephrotic syndrome and to determine whether excess urinary T4 excretion is present in other patients with proteinuria. We present data regarding the patient's initial presentation, diagnostic studies, and course of her illness. We suspected urinary T4 loss to be the cause of her presentation and analyzed her urine sample for total T4. We also analyzed differences in urinary T4 excretion in 22 patients with proteinuria and 16 control patients without proteinuria. Relevant medical literature is reviewed. A 44-year-old woman presented with a 3-month history of increasing fluid retention, weight gain, and fatigue. She had long-standing hypothyroidism on a stable levothyroxine dosage, 125 mcg/d. She had gained 27 kg and had developed significant edema. She had a grossly elevated thyroid-stimulating hormone level of 91 mIU/L. Her condition worsened, and a urinary protein measurement was 14.06 g/24 h-diagnostic of nephrotic syndrome. The levothyroxine dosage was increased to 225 mcg/d. Urinary total T4 concentration in a 24-hour sample was 59.0 microg/L (83.1 microg/24 h), indicating that a substantial fraction of her orally ingested T4 was lost in urine. Urinary total T4 excretion was significantly higher in patients with proteinuria (mean +/- standard deviation, 18.0 +/- 18.2 microg/L) vs control patients without proteinuria (mean, 3.8 +/- 1.8 microg/L) (P = .0014). In the patient described, urinary T4 loss due to proteinuria and nephrotic syndrome resulted in a severe exacerbation of underlying hypothyroidism.

Plasma thyroxine changes of the Apollo Crewman.

PubMed

Sheinfeld, M; Leach, C S; Johnson, P C

1975-01-01

Blood drawn from Apollo crew member; to the mission, at recovery, and postmission was used to examine the effect Apollo mission activities have on tyroid hormone levels. At recovery, statistically significant increases in thyroxine and the free thyroxine index were found. Serum cholesterol and triglycerides were decreased. No change of statistical significance was found in the T3 binding percentage, total serum proteins, and albumin. We conclude that apollo activities and environment caused the postmission increase in serum cholesterol may be one result of the increased thyroxine activity.

Rethinking the biological relationships of the thyroid hormones, l-thyroxine and 3,5,3'-triiodothyronine.

PubMed

Maher, Stacey K; Wojnarowicz, Pola; Ichu, Taka-Aki; Veldhoen, Nik; Lu, Linghong; Lesperance, Mary; Propper, Catherine R; Helbing, Caren C

2016-06-01

Thyroid hormones (THs), l-thyroxine (T4) and 3,5,3'-triiodothyronine (T3), are essential for vertebrate growth and development. Classically, T4 is 5'-deiodinated to the active hormone, T3, in target tissues which then binds nuclear TH receptors (TRs) and regulates gene transcription. However, it is possible that T4 acts directly on target tissues. Frog metamorphosis is a powerful TR-dependent model for studying TH action. Premetamorphic Rana (Lithobates) catesbeiana tadpoles were injected with 0.1-50 T3 or 0.5-250T4pmol/gbodyweight to account for their 5-fold difference in biological activity and the mRNA profiles in six tissues from well-characterized TH-responsive genes were evaluated after 48h using quantitative real time polymerase chain reaction. 5'-deiodinase-poor tissues should produce superimposable dose-response curves if T4 does not require conversion to T3. This was the case in lung and tail fin; the latter tissue recapitulating these responses in organ culture. 5'-deiodinase-rich tissues should convert T4 to T3. Because T3 has a higher affinity to TRs, a 5-fold higher T4 dose compared to T3 should produce greater transcript induction. This was observed in the brain and for most intestinal transcripts. However, some gene transcripts in the intestine and all transcripts in the back skin produced superimposable response curves suggesting that a direct mode of T4 action is plausible in these tissues. While the liver showed results consistent with its 5'-deiodinase-poor status, we found evidence of an alternate, non-genomic mechanism for two gene transcripts. Therefore, mechanisms not requiring T4 conversion to T3 may play a far greater role than previously thought. Copyright © 2016 Elsevier Inc. All rights reserved.

Thyroxine and triiodothyronine content in commercially available thyroid health supplements.

PubMed

Kang, Grace Y; Parks, Jonathan R; Fileta, Bader; Chang, Audrey; Abdel-Rahim, Maged M; Burch, Henry B; Bernet, Victor J

2013-10-01

As defined by the Dietary Supplement Health and Education Act 1997, such substances as herbs and dietary supplements fall under general Food and Drug Administration supervision but have not been closely regulated to date. We examined the thyroid hormone content in readily available dietary health supplements marketed for "thyroid support." Ten commercially available thyroid dietary supplements were purchased. Thyroid supplements were dissolved in 10 mL of acetonitrile and water with 0.1% trifloroacetic acid and analyzed using high-performance liquid chromatography for the presence of both thyroxine (T4) and triiodothyronine (T3) using levothyroxine and liothyronine as a positive controls and standards. The amount of T4 and T3 was measured separately for each supplement sample. Nine out of 10 supplements revealed a detectable amount of T3 (1.3-25.4 μg/tablet) and 5 of 10 contained T4 (5.77-22.9 μg/tablet). Taken at the recommended dose, 5 supplements delivered T3 quantities of greater than 10 μg/day, and 4 delivered T4 quantities ranging from 8.57 to 91.6 μg/day. The majority of dietary thyroid supplements studied contained clinically relevant amounts of T4 and T3, some of which exceeded common treatment doses for hypothyroidism. These amounts of thyroid hormone, found in easily accessible dietary supplements, potentially expose patients to the risk of alterations in thyroid levels even to the point of developing iatrogenic thyrotoxicosis. The current study results emphasize the importance of patient and provider education regarding the use of dietary supplements and highlight the need for greater regulation of these products, which hold potential danger to public health.

Retinal S-opsin dominance in Ansell's mole-rats (Fukomys anselli) is a consequence of naturally low serum thyroxine.

PubMed

Henning, Yoshiyuki; Mladěnková, Nella; Burda, Hynek; Szafranski, Karol; Begall, Sabine

2018-03-12

Mammals usually possess a majority of medium-wavelength sensitive (M-) and a minority of short-wavelength sensitive (S-) opsins in the retina, enabling dichromatic vision. Unexpectedly, subterranean rodents from the genus Fukomys exhibit an S-opsin majority, which is exceptional among mammals, albeit with no apparent adaptive value. Because thyroid hormones (THs) are pivotal for M-opsin expression and metabolic rate regulation, we have, for the first time, manipulated TH levels in the Ansell's mole-rat (Fukomys anselli) using osmotic pumps. In Ansell's mole-rats, the TH thyroxine (T4) is naturally low, likely as an adaptation to the harsh subterranean ecological conditions by keeping resting metabolic rate (RMR) low. We measured gene expression levels in the eye, RMR, and body mass (BM) in TH-treated animals. T4 treatment increased both, S- and M-opsin expression, albeit M-opsin expression at a higher degree. However, this plasticity was only given in animals up to approximately 2.5 years. Mass-specific RMR was not affected following T4 treatment, although BM decreased. Furthermore, the T4 inactivation rate is naturally higher in F. anselli compared to laboratory rodents. This is the first experimental evidence that the S-opsin majority in Ansell's mole-rats is a side effect of low T4, which is downregulated to keep RMR low.

Hyperthyroidism in four guinea pigs: clinical manifestations, diagnosis, and treatment.

PubMed

Künzel, F; Hierlmeier, B; Christian, M; Reifinger, M

2013-12-01

Hyperthyroidism was diagnosed in four guinea pigs by demonstration of an increased serum total thyroxine concentration. The main clinical signs were comparable with those observed in feline hyperthyroidism and included weight loss despite maintenance of appetite and a palpable mass in the ventral cervical region. Three animals were treated successfully with methimazole for between 13 and 28 months. Clinical signs and regular measurement of circulating total thyroxine concentrations appear to be convenient parameters for monitoring response to medical therapy. © 2013 British Small Animal Veterinary Association.

Local renin–angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy

PubMed Central

Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

2008-01-01

We have reported previously that thyroid hormone activates the circulating and tissue renin–angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin–angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin–angiotensin system in Sprague–Dawley rats was fixed by chronic angiotensin II infusion (40 ng/ min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0·1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0·12 ± 0·03 and 0·15 ± 0·03 μg/h per liter, 126 ± 5 and 130 ± 5 ng/l respectively) (means ± s.e.m.). Despite stabilization of the circulating renin–angiotensin system, thyroid hormone induced cardiac hypertrophy (5·0 ± 0·5 vs 3·5 ± 0·1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74 ± 2 vs 48 ± 2%, 6·5 ± 0·8 vs 3·8 ± 0·4 ng/h per g, 231 ± 30 vs 149 ± 2 pg/g respectively). These results indicate that the local renin–angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy. PMID:9854175

CE with chemiluminescence detection for the determination of thyroxine in human serum.

PubMed

Mu, Xiaomei; Li, Shuting; Lu, Xin; Zhao, Shulin

2014-04-01

A sensitive and rapid approach to perform thyroxine (T4) assay by CE with chemiluminescence (CL) detection was developed. The sensitive detection was based on the enhancement effect of T4 on the CL reaction between luminol and potassium permanganate (KMnO4 ) in alkaline solution. A laboratory-built reaction flow cell and a photon counter were deployed for the CL detection. Experimental conditions for CL detection were studied in detail to achieve maximum assay sensitivity. Optimal conditions were found to be 5.0 × 10(-4) M luminol added to the CE running buffer and 9.2 × 10(-5) M KMnO4 in 0.072 M NaOH solution introduced postcolumn. In the optimized experimental conditions, the linear range for T4 detection was 6.0 × 10(-8) -6.0 × 10(-6) M, with the detection limit of 2.0 × 10(-8) M (S/N = 3). Six human serum samples from healthy subjects, hyperthyroid patients and hypothyroid patients were analyzed by the presented method. The serum level of T4 in healthy subjects was found be 9.0 × 10(-8) M, whereas the T4 level was found to be 15.6 × 10(-8) M in hyperthyroid patients and 1.3 × 10(-8) M in hypothyroid patients. The results suggested a potential application of the proposed assay in rapid primary diagnosis of diseases such as hyperthyroid and hypothyroid. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Circulating Levels of Orexin-A, Nesfatin-1, Agouti-Related Peptide, and Neuropeptide Y in Patients with Hyperthyroidism.

PubMed

Tohma, Yusuf; Akturk, Mujde; Altinova, Alev; Yassibas, Emine; Cerit, Ethem Turgay; Gulbahar, Ozlem; Arslan, Metin; Sanlier, Nevin; Toruner, Fusun

2015-07-01

There is insufficient information about the appetite-related hormones orexin-A, nesfatin-1, agouti-related peptide (AgRP), and neuropeptide Y (NPY) in hyperthyroidism. The aim of the present study was to investigate the effects of hyperthyroidism on the basal metabolic rate (BMR) and energy intake, orexin-A, nesfatin-1, AgRP, NPY, and leptin levels in the circulation, and their relationship with each other and on appetite. In this prospective study, patients were evaluated in hyperthyroid and euthyroid states in comparison with healthy subjects. Twenty-one patients with overt hyperthyroidism and 33 healthy controls were included in the study. Daily energy intake in the hyperthyroid state was found to be higher than that in the euthyroid state patient group (p=0.039). BMR was higher in hyperthyroid patients than the control group (p=0.018). Orexin-A was lower and nesfatin-1 was higher in hyperthyroid patients compared to the controls (p<0.001), whereas orexin-A increased and nesfatin-1 decreased after euthyroidism (p=0.003, p<0.001). No differences were found in the AgRP, NPY, and leptin levels between the hyperthyroid and euthyroid states and controls (p>0.05). Orexin-A correlated negatively with nesfatin-1 (p=0.042), BMR (p=0.013), free triiodothyronine (fT3; p<0.001), and free thyroxine (fT4; p<0.001) and positively with thyrotropin (TSH; p<0.001). Nesfatin-1 correlated negatively with orexin-A (p=0.042) and TSH (p<0.001) and positively with fT3 (p=0.005) and fT4 (p=0.001). In the regression analysis, "diagnosis of hyperthyroidism" was the main factor affecting orexin-A (p<0.001). Although it seems that no relationship exists among orexin-A, nesfatin-1, and increased appetite in hyperthyroidism, the orexin-A and nesfatin-1 levels are markedly affected by hyperthyroidism.

Exogenous thyroxine improves glucose intolerance in insulin-resistant rats.

PubMed

Vazquez-Anaya, Guillermo; Martinez, Bridget; Soñanez-Organis, José G; Nakano, Daisuke; Nishiyama, Akira; Ortiz, Rudy M

2017-03-01

Both hypothyroidism and hyperthyroidism are associated with glucose intolerance, calling into question the contribution of thyroid hormones (TH) on glucose regulation. TH analogues and derivatives may be effective treatment options for glucose intolerance and insulin resistance (IR), but their potential glucoregulatory effects during conditions of impaired metabolism are not well described. To assess the effects of thyroxine (T 4 ) on glucose intolerance in a model of insulin resistance, an oral glucose tolerance test (oGTT) was performed on three groups of rats (n = 8): (1) lean, Long Evans Tokushima Otsuka (LETO), (2) obese, Otsuka Long Evans Tokushima Fatty (OLETF) and (3) OLETF + T 4 (8.0 µg/100 g BM/day × 5 weeks). T 4 attenuated glucose intolerance by 15% and decreased IR index (IRI) by 34% in T 4 -treated OLETF compared to untreated OLETF despite a 31% decrease in muscle Glut4 mRNA expression. T 4 increased the mRNA expressions of muscle monocarboxylate transporter 10 (Mct10), deiodinase type 2 (Di2), sirtuin 1 (Sirt1) and uncoupling protein 2 (Ucp2) by 1.8-, 2.2-, 2.7- and 1.4-fold, respectively, compared to OLETF. Activation of AMP-activated protein kinase (AMPK) and insulin receptor were not significantly altered suggesting that the improvements in glucose intolerance and IR were independent of enhanced insulin-mediated signaling. The results suggest that T 4 treatment increased the influx of T 4 in skeletal muscle and, with an increase of DI2, increased the availability of the biologically active T 3 to upregulate key factors such SIRT1 and UCP2 involved in cellular metabolism and glucose homeostasis. © 2017 Society for Endocrinology.

The role of maternal thyroid hormones on the development of the brushtail possum, Trichosurus vulpecula.

PubMed

Gemmell, R T; Buaboocha, W

1998-01-01

Thyroxine (T4) is a vital hormone for the development of mammals. To determine the role of maternal thyroid hormones on organ development, methimazole, an inhibitor of T4, was first administered via a minipump to 13 mothers with pouch young between days 10 and 80 post partum for 28 days. Three young survived and 10 of the young died at 104.0 +/- 10.8 days post partum (mean, SEM). Methimazole was then administered for 28 days to 6 lactating adult possums with pouch young at day 20 post partum. The effects of this treatment on the maternal plasma concentrations of T4 were monitored and the development of the lung, kidney and brain of the young were examined at day 90 post partum. There was no difference in the morphology of the lung, kidney and brain of pouch young at day 90 post partum whose mothers were treated with methimazole or saline. Thus methimazole administered to lactating possums for a short period early in lactation can cause the demise of the young about day 100 post partum although the cause of death is unknown. It is possible that the development of the central nervous system or some other vital organ has been inhibited, this altered state not being apparent morphologically. Nevertheless the marsupial appears to be similar to the eutherian in its requirement for thyroxine for normal development. However whereas this requirement is apparent during fetal development and around the time of birth in eutherians thyroxine is of importance during pouch development in marsupials.

Severe Hypothyroidism due to the Loss of Therapeutic Efficacy of l-Thyroxine in a Patient with Esophageal Complication Associated with Systemic Sclerosis.

PubMed

Lobasso, Antonio; Nappi, Liliana; Barbieri, Letizia; Peirce, Carmela; Ippolito, Serena; Arpaia, Debora; Rossi, Francesca Wanda; de Paulis, Amato; Biondi, Bernadette

2017-01-01

Thyroid function abnormalities and thyroid autoantibodies have been frequently described in patients with systemic autoimmune diseases as systemic sclerosis (SSc). Serum TSH levels are higher in SSc patients with more severe skin diseases and a worse modified Rodnan skin score. Asymptomatic esophageal involvement due to SSc has never been described as a cause of severe hypothyroidism due to l-thyroxine (l-T4) malabsorption in patients with Hashimoto's thyroiditis (HT) and SSc. Here, we report a case of a 56-year-old female affected by both SSc and HT who developed severe hypothyroidism due to the loss of therapeutic efficacy of l-T4. Therapeutic failure resulted from the altered l-T4 absorption because of SSc esophageal complications. Clinical findings improved after the administration of oral liquid l-T4. Thyroid function completely normalized with a full clinical recovery, the disappearance of the pericardial effusion and the improvement of the pulmonary pressure. A recognition of a poor absorption is crucial in patients with hypothyroidism and SSc to reduce the risk of the subsequent adverse events. This case suggests the importance of clinical and laboratory surveillance in patients with SSc and HT because the systemic complications of these dysfunctions may worsen the prognosis of hypothyroid SSc/HT patients.

The effect of severe starvation and captivity stress on plasma thyroxine and triiodothyronine concentrations in an antarctic bird (emperor penguin).

PubMed

Groscolas, R; Leloup, J

1989-01-01

The effect of confinement and severe starvation on the plasma thyroxine (T4) and triiodothyronine (T3) concentrations was determined in emperor penguins (Aptenodytes forsteri). During their annual cycle, emperor penguins fast freely for periods of up to 4 months and may thus represent a unique subject to study endocrine adaptations to fasting. Plasma T4 concentrations progressively decreased following capture and confinement of naturally fasting penguins, and within 15-20 days stabilized at levels three times lower than in free-living penguins. A transient fourfold increase in plasma T3 concentration developed within the day following confinement in parallel with a rise in daily body mass loss. Both plasma T3 concentration and mass loss subsided to normal levels within 15 days. The decrease in plasma T4 concentration is in accordance with the well-known inhibitory effect of stress on thyroid function in birds and mammals, whereas the transient increase in plasma T3 concentration seems related to enhancement of energy expenditure as a consequence of restlessness. Starvation severe enough to exhaust fat stores and to activate protein catabolism induced a 6- and 5 to 10-fold fall in plasma T4 and T3, respectively. This is in marked contrast with maintenance of plasma thyroid levels during long-term natural fasting associated with protein sparing (R. Groscolas and J. Leloup (1986) Gen. Comp. Endocrinol. 63, 264-274). Surprisingly, there was a final reincrease in plasma T4 concentration in very lean penguins. These results suggest that the effect of starvation on plasma thyroid hormones seems to depend on how much protein catabolism is activated and demonstrate the acute sensitivity of thyroid hormone balance to stress in penguins.

Effect of feeding and temperature on the circadian rhythms of cortisol, thyroxine and triiodothyronine in pigs

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

Becker, B.A.; Nienaber, J.A.; Ford, J.J.

1986-03-05

An experiment was conducted to evaluate the circadian rhythms of cortisol, thyroxine (T/sub 4/) and triiodothyronine (T/sub 3/) in pigs under two temperature and feeding regimes. Twenty-eight barrows were randomly assigned to one of the following: 1) ad-libitum fed at 5/sup 0/C(AL-5); 2) ad-libitum fed at 20/sup 0/C(AL-20); 3) meal fed at 5/sup 0/C(M-5); and 4) meal fed at 20/sup 0/C(M-20). M-5 and M-20 animals were fed at 0730 and 1400 hrs. Lights were on from 0600 to 2000 hrs. After 5 wks, blood samples were collected for 27 hrs. Serum cortisol, T/sub 4/ and T/sub 3/ concentrations were determinedmore » by RIA. No significant differences were found in the mesors, amplitudes or acrophases for cortisol. The mesors for T/sub 4/ (p<.01) were 60.6 +/- 5.6, 40.2 +/- 5.6, 61.2 +/- 5.6 and 49.1 +/- 5.0 ng/ml for AL-5, AL-20, M-5, and M-20, respectively. The mesors for T/sub 3/ (p<.01) were .85 +/- .06, .69 +/- .06, .92 +/- .06 and .66 +/- .05 ng/ml for AL-5, AL-20, M-5, and M-20 respectively. No differences in the amplitudes or acrophases for T/sub 3/ or T/sub 4/ were found. These data show that temperature and feeding regimes do not entrain the circadian rhythm of cortisol in pigs. The circadian rhythms of T/sub 4/ and T/sub 3/ are also not altered by feeding regimes but are affected by temperature.« less

Differential involvement of various sources of reactive oxygen species in thyroxin-induced hemodynamic changes and contractile dysfunction of the heart and diaphragm muscles

PubMed Central

Elnakish, Mohammad T.; Schultz, Eric J.; Gearinger, Rachel L.; Saad, Nancy S.; Rastogi, Neha; Ahmed, Amany A.E.; Mohler, Peter J.; Janssen, Paul M.L.

2015-01-01

Thyroid hormones are key regulators of basal metabolic state and oxidative metabolism. Hyperthyroidism has been reported to cause significant alterations in hemodynamics, and in cardiac and diaphragm muscle function, all of which have been linked to increased oxidative stress. However, the definite source of increased reactive oxygen species (ROS) in each of these phenotypes is still unknown. The goal of the current study was to test the hypothesis that thyroxin (T4) may produce distinct hemodynamic, cardiac, and diaphragm muscle abnormalities by differentially affecting various sources of ROS. Wild-type and T4 mice with and without 2-week treatments with allopurinol (xanthine oxidase inhibitor), apocynin (NADPH oxidase inhibitor), L-NIO (nitric oxide synthase inhibitor), or MitoTEMPO (mitochondria-targeted antioxidant) were studied. Blood pressure and echocardiography were noninvasively evaluated, followed by ex vivo assessments of isolated heart and diaphragm muscle functions. Treatment with L-NIO attenuated the T4-induced hypertension in mice. However, apocynin improved the left-ventricular (LV) dysfunction without preventing the cardiac hypertrophy in these mice. Both allopurinol and MitoTEMPO reduced the T4-induced fatigability of the diaphragm muscles. In conclusion, we show here for the first time that T4 exerts differential effects on various sources of ROS to induce distinct cardiovascular and skeletal muscle phenotypes. Additionally, we find that T4-induced LV dysfunction is independent of cardiac hypertrophy and NADPH oxidase is a key player in this process. Furthermore, we prove the significance of both xanthine oxidase and mitochondrial ROS pathways in T4-induced fatigability of diaphragm muscles. Finally, we confirm the importance of the nitric oxide pathway in T4-induced hypertension. PMID:25795514

Thyroid function and neuropsychological status in older adults.

PubMed

Shrestha, Srishti; Bloom, Michael S; Yucel, Recai; Seegal, Richard F; Rej, Robert; McCaffrey, Robert J; Fitzgerald, Edward F

2016-10-01

Overt thyroid dysfunction is recognized as a risk factor for neuropsychological deficits in aging populations, yet evidence for how changes in levels of circulatory thyroid hormones impact specific neuropsychological domains is limited. Here we report cross-sectional associations between serum thyroid hormone concentrations and several neuropsychological function domains among men and women aged 55-74years. We administered neuropsychological tests to assess memory, learning, executive function, measures of attention, visuospatial function, affective state, and motor function. Multivariable linear regression analyses were performed adjusting for age, sex, education, and cigarette smoking. Effects were reported as differences in test scores per one interquartile range (IQR) increase in hormone concentration. Higher total thyroxine (T4) and free thyroxine (fT4) were associated with improved visuospatial function, as measured by Block Design Subtest total scores; associated increments per IQR differences in T4 and fT4 were 15% and 19%, respectively (false discovery rate q-values <0.05). We also detected statistical interactions between age and fT4 for effects in tasks of memory and learning. Concurrent increases in age and fT4 were associated with deficits in memory and learning as measured by California Verbal Learning Test subtests (10% and 16% deficits in t-score and short delay free recall score, respectively). Our findings suggest that changes in thyroid hormones may have important implications for neuropsychological function in aging populations. Further large-scale studies with comprehensive thyroid function and neuropsychological outcome assessments are warranted to confirm these results. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative study on 2,2′,4,5,5′-pentachlorobiphenyl-mediated decrease in serum thyroxine level between C57BL/6 and its transthyretin-deficient mice

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

Kato, Yoshihisa, E-mail: kato@kph.bunri-u.ac.jp; Tamaki, Sekihiro; Haraguchi, Koichi

The relationships between the changes in the levels of serum total thyroxine (T{sub 4}), serum T{sub 4}-transthyretin (TTR) complex, and accumulation of T{sub 4} in tissues by 2,2′,4,5,5′-pentachlorobiphenyl (PentaCB) were examined using wild-type C57BL/6 (WT) and its TTR-deficient (TTR-null) mice. The constitutive level of serum total T{sub 4} was much higher in WT mice than in TTR-null mice. In WT mice 4 days after a single intraperitoneal injection with PentaCB (112 mg/kg), serum total T{sub 4} level was significantly decreased along with a decrease in serum T{sub 4}–TTR complex, and the levels of serum total T{sub 4} in the PentaCB-treatedmore » WT mice were almost the same to those in PentaCB-untreated (control) TTR-null mice. In addition, a slight decrease in serum total T{sub 4} by PentaCB treatment was observed in TTR-null mice. Furthermore, clearance of [{sup 125}I]T{sub 4} from the serum after [{sup 125}I]T{sub 4}-administration was promoted by the PentaCB-pretreatment in either strain of mice, especially WT mice. On the other hand, accumulation level of [{sup 125}I]T{sub 4} in the liver, but not in extrahepatic tissues, was strikingly enhanced in the PentaCB-pretreated WT and TTR-null mice. Furthermore, in both strains of mice, PentaCB-pretreatment led to significant increases in the steady-state distribution volume of [{sup 125}I]T{sub 4} and the concentration ratio of the liver to serum. The present findings demonstrate that PentaCB-mediated decrease in serum T{sub 4} level occurs mainly through increase in accumulation level of T{sub 4} in the liver and further indicate that the increased accumulation of T{sub 4} in the liver of WT mice is primarily dependent on the PentaCB-mediated inhibition of serum T{sub 4}–TTR complex formation.« less

Sex-steroid and thyroid hormone concentrations in juvenile alligators (Alligator mississippiensis) from contaminated and reference lakes in Florida, USA

USGS Publications Warehouse

Grain, D.A.; Guillette, L.J.; Pickford, D.B.; Percival, H.F.; Woodward, A.R.

1998-01-01

Sex-steroid and thyroid hormones are critical regulators of growth and reproduction in all vertebrates, and several recent studies suggest that environmental chemicals can alter circulating concentrations of these hormones. This study examines plasma concentrations of estradiol-171?? (E2), testosterone (T), triiodothyronine (T3), and thyroxine (T4) in juvenile alligators (60-140 cm total length) from two contaminated lakes and one reference lake in Florida. First, the data were analyzed by comparing hormone concentrations among males and females from the different lakes. Whereas there were no differences in plasma E2 concentrations among animals of the three lakes, male alligators from the contaminated lakes (Lake Apopka and Lake Okeechobee) had significantly lower plasma T concentrations compared 10 males from the reference take (Lake Woodruff). Concentrations of thyroid hormones also differed in animals of the three lakes, with T4 concentrations being elevated in Lake Okeechobee males compared to Lake Woodruff males. Second, the relationship between body size and hormone concentration was examined using regression analysis. Most notably for steroid hormones, no clear relationship was detected between E2 and total length in Apopka females (r2 0.09, p = 0.54) or between T and total length in Apopka males (r2 = 0.007, p = 0.75). Females from Apopka (r2 = 0.318, p = 0.09) and Okeechobee (r2 = 0.222, p = 0.09) exhibited weak correlations between T3 and total length. Males from Apopka (r2 = 0.015, p = 0.66) and Okeechobee (r2 = 0.128, p = 0.19) showed no correlation between T4 and total length. These results indicate: some of the previously reported abnormalities in steroid hormones of hatchling alligators persist, at least, through the juvenile years; steroid and thyroid hormones are related to body size in juvenile alligators from the reference lake, whereas alligators living in lakes Apopka and Okeechobee experience alterations in circulating thyroid and steroid hormones in relationship to body size; and a number of the hormone abnormalities reported previously for Lake Apopka alligators are observed in alligators from Lake Okeechobee - a lake associated with numerous contaminant sources but no major chemical spill. The endocrine alterations reported in this study are hypothesized to be a response to embryonic exposure to endocrine-disrupting contaminants.

Influence of maternal hyperthyroidism in the rat on the expression of neuronal and astrocytic cytoskeletal proteins in fetal brain.

PubMed

Evans, I M; Pickard, M R; Sinha, A K; Leonard, A J; Sampson, D C; Ekins, R P

2002-12-01

Maternal hypothyroidism during pregnancy impairs brain function in human and rat offspring, but little is known regarding the influence of maternal hyperthyroidism on neurodevelopment. We have previously shown that the expression of neuronal and glial differentiation markers in fetal brain is compromised in hypothyroid rat dam pregnancies and have now therefore extended this investigation to hyperthyroid rat dams. Study groups comprised partially thyroidectomised dams, implanted with osmotic pumps infusing either vehicle (TX dams) or a supraphysiological dose of thyroxine (T4) (HYPER dams), and euthyroid dams infused with vehicle (N dams). Cytoskeletal protein abundance was determined in fetal brain at 21 days of gestation by immunoblot analysis. Relative to N dams, circulating total T4 levels were reduced to around one-third in TX dams but were doubled in HYPER dams. Fetal brain weight was increased in HYPER dams, whereas litter size and fetal body weight were reduced in TX dams. Glial fibrillary acidic protein expression was similar in HYPER and TX dams, being reduced in both cases relative to N dams. alpha-Internexin (INX) abundance was reduced in HYPER dams and increased in TX dams, whereas neurofilament 68 (NF68) exhibited increased abundance in HYPER dams. Furthermore, INX was inversely related to - and NF68 directly related to - maternal serum total T4 levels, independently of fetal brain weight. In conclusion, maternal hyperthyroidism compromises the expression of neuronal cytoskeletal proteins in late fetal brain, suggestive of a pattern of accelerated neuronal differentiation.

Effects of an iodine-restricted food on client-owned cats with hyperthyroidism.

PubMed

van der Kooij, Marieke; Bečvářová, Iveta; Meyer, Hein P; Teske, Erik; Kooistra, Hans S

2014-06-01

The objective of this prospective, multicentre, non-controlled, open-label study was to evaluate the effects of an iodine-restricted food on circulating total thyroxine (TT4) concentrations and clinical parameters in client-owned cats with hyperthyroidism. Two hundred and twenty-five cats were enrolled in the study and adapted to the iodine-restricted food. Data from physical examinations, questionnaires completed by veterinarians and owners, and circulating concentrations of TT4, urea and creatinine were recorded at weeks 0, 4 and 8. The study group included 136 female and 89 male cats (median age 15 years, range 4-21 years). Group 1 (n = 113) had been on previous anti-thyroid medication, while group 2 (n = 112) consisted of newly diagnosed cats. No differences were found between the two groups at any time point. Circulating TT4 concentrations had decreased (P <0.0001) at week 4 and did not change significantly from week 4 to week 8. Circulating TT4 concentration was within the reference range in 56/88 cats at week 4 and in 51/68 cats at week 8. Clinical parameters (vomiting, polyuria, polydipsia, hyperactivity, polyphagia, weight loss, hair coat quality, and quality of life) had improved (P <0.0001) by week 4. Circulating creatinine concentration decreased (P = 0.001) from week 0 to week 4. Side effects associated with feeding the iodine-restricted food were not observed. In conclusion, in client-owned cats with hyperthyroidism an iodine-restricted food is a valuable management option to normalise circulating TT4 concentrations, and improve clinical signs of hyperthyroidism within 4 weeks. This applies to newly diagnosed cats, as well as to previously diagnosed cats receiving anti-thyroid drugs. © ISFM and AAFP 2013.

Assessment of the binding of hydroxylated polybrominated diphenyl ethers to thyroid hormone transport proteins using a site-specific fluorescence probe.

PubMed

Ren, Xiao M; Guo, Liang-Hong

2012-04-17

Polybrominated diphenyl ethers (PBDEs) have been shown to disrupt thyroid hormone (TH) functions on experimental animals, and one of the proposed disruption mechanisms is the competitive binding of PBDE metabolites to TH transport proteins. In this report, a nonradioactive, site-specific fluorescein-thyroxine (F-T4) conjugate was designed and synthesized as a fluorescence probe to study the binding interaction of hydroxylated PBDEs to thyroxine-binding globulin (TBG) and transthyretin (TTR), two major TH transport proteins in human plasma. Compared with free F-T4, the fluorescence intensity of TTR-bound conjugate was enhanced by as much as 2-fold, and the fluorescence polarization value of TBG-bound conjugate increased by more than 20-fold. These changes provide signal modulation mechanisms for F-T4 as a fluorescence probe. Based on fluorescence quantum yield and lifetime measurements, the fluorescence intensity enhancement was likely due to the elimination of intramolecular fluorescence quenching of fluorescein by T4 after F-T4 was bound to TTR. In circular dichroism and intrinsic tryptophan fluorescence measurements, F-T4 induced similar spectroscopic changes of the proteins as T4 did, suggesting that F-T4 bound to the proteins at the T4 binding site. By using F-T4 as the fluorescence probe in competitive binding assays, 11 OH-PBDEs with different levels of bromination and different hydroxylation positions were assessed for their binding affinity with TBG and TTR, respectively. The results indicate that the binding affinity generally increased with bromine number and OH position also played an important role. 3-OH-BDE-47 and 3'-OH-BDE-154 bound to TTR and TBG even stronger, respectively, than T4. With rising environmental level and high bioaccumulation capability, PBDEs have the potential to disrupt thyroid homeostasis by competitive binding with TH transport proteins.

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

PubMed

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

2000-03-01

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

Humoral and Cellular Immune Response in Canine Hypothyroidism.

PubMed

Miller, J; Popiel, J; Chełmońska-Soyta, A

2015-07-01

Hypothyroidism is one of the most common endocrine diseases in dogs and is generally considered to be autoimmune in nature. In human hypothyroidism, the thyroid gland is destroyed by both cellular (i.e. autoreactive helper and cytotoxic T lymphocytes) and humoral (i.e. autoantibodies specific for thyroglobulin, thyroxine and triiodothyronine) effector mechanisms. Other suggested factors include impaired peripheral immune suppression (i.e. the malfunction of regulatory T cells) or an additional pro-inflammatory effect of T helper 17 lymphocytes. The aim of this study was to evaluate immunological changes in canine hypothyroidism. Twenty-eight clinically healthy dogs, 25 hypothyroid dogs without thyroglobulin antibodies and eight hypothyroid dogs with these autoantibodies were enrolled into the study. There were alterations in serum proteins in hypothyroid dogs compared with healthy controls (i.e. raised concentrations of α-globulins, β2- and γ-globulins) as well as higher concentration of acute phase proteins and circulating immune complexes. Hypothyroid animals had a lower CD4:CD8 ratio in peripheral blood compared with control dogs and diseased dogs also had higher expression of interferon γ (gene and protein expression) and CD28 (gene expression). Similar findings were found in both groups of hypothyroid dogs. Canine hypothyroidism is therefore characterized by systemic inflammation with dominance of a cellular immune response. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influence of L-thyroxine administration on poor-platelet plasma VEGF concentrations in patients with induced short-term hypothyroidism, monitored for thyroid carcinoma.

PubMed

Dedecjus, Marek; Kołomecki, Krzysztof; Brzeziński, Jan; Adamczewski, Zbigniew; Tazbir, Józef; Lewiński, Andrzej

2007-02-01

Angiogenesis is a process of new blood vessel development from pre-existing vasculature. It is a crucial process in normal physiology, as well as in several pathological conditions. The vascular endothelial growth factor (VEGF) represents a family of specific endothelial cell mitogens, involved in normal angiogenesis and in tumour development. The aim of the present study was to estimate the influence of L-thyroxine (L-T4) administration on poor-platelet plasma (P-PP) VEGF concentrations in patients with induced short-term hypothyroidism, monitored for differentiated thyroid carcinoma. In the present study, P-PP concentrations of VEGF, thyroglobulin, thyrotropin and free thyroid hormones were investigated in a population of 24 hypothyroid patients, who were withdrawn from L-T4 treatment for 5 weeks and studied before and after 2 months of L-T4 therapy. Only healthy female patients with no evidence of metastasis in whole body scintigraphy were included in the study. They were then compared with 20 healthy control subjects, matched for age, sex and body mass index (BMI). The patients had significantly lower plasma VEGF concentrations before treatment with L-T4 than after administration of that hormone. There was no significant difference in plasma VEGF levels, either between the patients treated with L-T4, and the controls, or between the patients untreated with L-T4, and the controls. Even short-time changes in thyrometabolic profile exert an important influence on P-PP VEGF concentrations, even if there is no thyroid tissue.

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

The effects of xylanase supplementation on growth, digestion, circulating hormone and metabolite levels, immunity and gut microflora in cockerels fed on wheat-based diets.

PubMed

Gao, F; Jiang, Y; Zhou, G H; Han, Z K

2007-08-01

1. The xylanase product used in this study was derived from a genetically modified isolate of Aspergillus niger. Two trials were conducted to investigate the effects of xylanase supplementation on growth, digestion, circulating hormone and metabolite levels, immune parameters and composition of the gut microflora in cockerels fed on wheat-based diets. 2. The experimental diets consisted of a wheat-based control diet supplemented with 0 or 0.1% enzyme preparation. The diets were fed between 7 and 21 d of age. 3. Enzyme supplementation improved growth and feed conversion efficiency. The addition of enzyme to wheat-based diet increased the apparent total digestibility of dry matter (DM), crude protein and fat. 4. Enzyme supplementation reduced the relative weight of digestive organs to a certain extent, but there was no significant difference. Enzyme supplementation reduced digesta viscosity in the jejunum. There was no significant difference between the two experimental groups in counts of lactobacillus and coliform bacteria in the caeca. 5. Enzyme supplementation increased the concentration of blood thyroxine (T(4)), insulin-like growth factor I (IGF-I) and insulin, reduced the concentrations of blood uric acid, but had no significant effect on the concentrations of blood glucose and triiodothyronine (T(3)). 6. Enzyme supplementation increased the relative weight of spleen of cockerels, serum antibody titres to Newcastle disease virus (NDV), lymphocyte proliferation in response to phytohaemagglutinin (PHA) and the natural killer (NK) cell activity. 7. It is concluded that supplementation with an enzyme preparation (xylanase), which hydrolyses non-starch polysaccharides can improve growth in cockerels fed on wheat-based diets. This improvement is achieved through enzyme effects on digestion, absorption, metabolism and immunity of cockerels.

Thyroid hormones and menstrual cycle function in a longitudinal cohort of premenopausal women.

PubMed

Jacobson, Melanie H; Howards, Penelope P; Darrow, Lyndsey A; Meadows, Juliana W; Kesner, James S; Spencer, Jessica B; Terrell, Metrecia L; Marcus, Michele

2018-05-01

Previous studies have reported that hyperthyroid and hypothyroid women experience menstrual irregularities more often compared with euthyroid women, but reasons for this are not well-understood and studies on thyroid hormones among euthyroid women are lacking. In a prospective cohort study of euthyroid women, this study characterised the relationship between thyroid hormone concentrations and prospectively collected menstrual function outcomes. Between 2004-2014, 86 euthyroid premenopausal women not lactating or taking hormonal medications participated in a study measuring menstrual function. Serum thyroid hormones were measured before the menstrual function study began. Women then collected first morning urine voids and completed daily bleeding diaries every day for three cycles. Urinary oestrogen and progesterone metabolites (estrone 3-glucuronide (E 1 3G) and pregnanediol 3-glucuronide (Pd3G)) and follicle-stimulating hormone were measured and adjusted for creatinine (Cr). Total thyroxine (T 4 ) concentrations were positively associated with Pd3G and E 1 3G. Women with higher (vs lower) T 4 had greater luteal phase maximum Pd3G (Pd3G = 11.7 μg/mg Cr for women with high T 4 vs Pd3G = 9.5 and 8.1 μg/mg Cr for women with medium and low T 4 , respectively) and greater follicular phase maximum E 1 3G (E 1 3G = 41.7 ng/mg Cr for women with high T 4 vs E 1 3G = 34.3 and 33.7 ng/mg Cr for women with medium and low T 4 , respectively). Circulating thyroid hormone concentrations were associated with subtle differences in menstrual cycle function outcomes, particularly sex steroid hormone levels in healthy women. Results contribute to the understanding of the relationship between thyroid function and the menstrual cycle, and may have implications for fertility and chronic disease. © 2018 John Wiley & Sons Ltd.

Biochemical changes after subchronic and chronic interaction of Schistosoma mansoni infection in Swiss albino mice with two specific compounds.

PubMed

Hanna, Laila S; Medhat, Amina M; Abdel-Menem, Hanan A

2003-04-01

In Egypt, infection with Schistosoma mansoni (S.m.) and residues of pesticides have been considered as major environmental pollutants that adversely affect health. Effects of diazinon (DZN) and/or praziquantel (PZQ) on the levels of plasma triiodothyronine (T3), thyroxine (T4), activities of brain acetylcholinesterase (AchE) and liver alanine aminotransferase (ALT) in addition to blood reduced glutathione (GSH) in healthy and S.m. infected mice were investigated after 9 and 17 weeks of either infection or intoxication with DZN. Triiodothyronine showed significant differences among the different treatments. The group of mice treated with PZQ showed the highest levels of T3 at both time intervals. Thyroxine level showed significant differences between the two time intervals. The lowest levels of T4 were observed in the infected-PZQ group at week 17. The maximum inhibition of brain AchE activity was noticed in DZN-PZQ treated group after 9 and 17 weeks. The different treatments significantly reduced the activities of liver ALT. The highest decrease was recorded in the infected-DZN-PZQ group at week 9. All treatments significantly lowered the levels of blood GSH after 9 weeks.

Effects of larval-juvenile treatment with perchlorate and co-treatment with thyroxine on zebrafish sex ratios

USGS Publications Warehouse

Mukhi, S.; Torres, L.; Patino, R.

2007-01-01

The objective of this study was to determine the effect of larval-juvenile exposure to perchlorate, a thyroid hormone synthesis inhibitor, on the establishment of gonadal sex ratios in zebrafish. Zebrafish were exposed to untreated water or water containing perchlorate at 100 or 250 ppm for a period of 30 days starting at 3 days postfertilization (dpf). Recovery treatments consisted of a combination of perchlorate and exogenous thyroxine (T4; 10 nM). Thyroid histology was assessed at the end of the treatment period (33 dpf), and gonadal histology and sex ratios were determined in fish that were allowed an additional 10-day period of growth in untreated water. As expected, exposure to perchlorate caused changes in thyroid histology consistent with hypothyroidism and these effects were reversed by co-treatment with exogenous T4. Perchlorate did not affect fish survival but co-treatment with T4 induced higher mortality. However, relative to the corresponding perchlorate concentration, co-treatment with T4 caused increased mortality only at a perchlorate concentration of 100 ppm. Perchlorate alone or in the presence of T4 suppressed body length at 43 dpf relative to control values. Perchlorate exposure skewed the sex ratio toward female in a concentration-dependent manner, and co-treatment with T4 not only blocked the feminizing effect of perchlorate but also overcompensated by skewing the sex ratio towards male. Moreover, co-treatment with T4 advanced the onset of spermatogenesis in males. There was no clear association between sex ratios and larval survival or growth. We conclude that endogenous thyroid hormone plays a role in the establishment of gonadal sex phenotype during early development in zebrafish. ?? 2006 Elsevier Inc. All rights reserved.

Thyroxine differentially modulates the peripheral clock: lessons from the human hair follicle.

PubMed

Hardman, Jonathan A; Haslam, Iain S; Farjo, Nilofer; Farjo, Bessam; Paus, Ralf

2015-01-01

The human hair follicle (HF) exhibits peripheral clock activity, with knock-down of clock genes (BMAL1 and PER1) prolonging active hair growth (anagen) and increasing pigmentation. Similarly, thyroid hormones prolong anagen and stimulate pigmentation in cultured human HFs. In addition they are recognized as key regulators of the central clock that controls circadian rhythmicity. Therefore, we asked whether thyroxine (T4) also influences peripheral clock activity in the human HF. Over 24 hours we found a significant reduction in protein levels of BMAL1 and PER1, with their transcript levels also decreasing significantly. Furthermore, while all clock genes maintained their rhythmicity in both the control and T4 treated HFs, there was a significant reduction in the amplitude of BMAL1 and PER1 in T4 (100 nM) treated HFs. Accompanying this, cell-cycle progression marker Cyclin D1 was also assessed appearing to show an induced circadian rhythmicity by T4 however, this was not significant. Contrary to short term cultures, after 6 days, transcript and/or protein levels of all core clock genes (BMAL1, PER1, clock, CRY1, CRY2) were up-regulated in T4 treated HFs. BMAL1 and PER1 mRNA was also up-regulated in the HF bulge, the location of HF epithelial stem cells. Together this provides the first direct evidence that T4 modulates the expression of the peripheral molecular clock. Thus, patients with thyroid dysfunction may also show a disordered peripheral clock, which raises the possibility that short term, pulsatile treatment with T4 might permit one to modulate circadian activity in peripheral tissues as a target to treat clock-related disease.

AN ITALIAN SURVEY OF COMPLIANCE WITH MAJOR GUIDELINES FOR L-THYROXINE OF PRIMARY HYPOTHYROIDISM.

PubMed

Vezzani, Silvia; Giannetta, Elisa; Altieri, Barbara; Barbonetti, Arcangelo; Bellastella, Giuseppe; Certo, Rosaria; Cignarelli, Angelo; Cinti, Francesca; D'Andrea, Settimio; Di Dalmazi, Giulia; Frara, Stefano; Garelli, Silvia; Giuffrida, Giuseppe; Maiorino, Maria Ida; Mele, Chiara; Mezza, Teresa; Pani, Maria Grazia; Samà, Maria Teresa; Satta, Chiara; Santi, Daniele

2018-05-01

The adherence by endocrinologists to guideline regarding levothyroxine (LT4) therapy and the compliance of patients may impact the management of hypothyroidism. The aim of this study was to compare the adherence of Italian endocrinologists to the ATA/AACE and ETA guidelines on the management of newly diagnosed primary hypothyroidism and to validate the Italian version of the Morisky-Green Medical Adherence Scale-8 (MMAS-8) questionnaire as applied to the evaluation of the adherence of patients with hypothyroidism to LT4 treatment. This was an observational, longitudinal, multicenter, cohort study, involving 12 Italian Units of Endocrinology. The study enrolled 1,039 consecutive outpatients (mean age 48 years; 855 women, 184 men). The concordance of Italian endocrinologists with American Association of Clinical Endocrinologists/American Thyroid Association (AACE/ATA) and European Thyroid Association (ETA) recommendations was comparable (77.1% and 71.7%) and increased (86.7 and 88.6%) after the recommendations on LT4 dose were excluded, considering only the remaining recommendations on diagnosis, therapy, and follow-up. The MMAS-8 was filled out by 293 patients. The mean score was 6.71 with 23.9% low (score <6), 38.6% medium (6 to <8), 37.5% highly (= 8) adherers; the internal validation coefficient was 0.613. Highly adherent patients were not more likely to have good control of hypothyroidism compared with either medium (69% versus 72%, P = .878) or low (69% versus 43%, P = .861) adherers. Clinical management of hypothyroidism in Italy demonstrated an observance of international guidelines by Italian endocrinologists. Validation of the Italian version of the MMAS-8 questionnaire provides clinicians with a reliable and simple tool for assessing the adherence of patients to LT4 treatment. AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; EDIPO = Endotrial SIE: DIagnosis and clinical management of Primitive hypothyrOidism in Italy; eCRF = electronic case report form; ETA = European Thyroid Association; fT3 = free triiodothyronine; fT4 = free thyroxine; LT4 = levothyroxine; MMAS-8 = Morisky-Green Medical Adherence Scale-8; PH = primary hypothyroidism; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone; US = ultrasonography.

Development of the larval amphibian growth and development ...

EPA Pesticide Factsheets

The Larval Amphibian Growth and Development Assay (LAGDA) is a Tier II test guideline being developed by the US Environmental Protection Agency under the Endocrine Disruptor Screening Program. The LAGDA was designed to evaluate effects of chronic chemical exposure on growth, thyroid-mediated amphibian metamorphosis and reproductive development. To evaluate the assay’s performance, two model chemicals targeting the hypothalamic-pituitary-gonadal (HPG) axis were tested; a weak estrogen receptor agonist, 4-tert-octylphenol (tOP), and an androgen receptor agonist, 17β-trenbolone (TB). Xenopus laevis embryos were constantly exposed in flow-through conditions to various test concentrations of tOP (nominal: 6.25, 12.5, 25, 50 μg/L) or TB (nominal: 12.5, 25, 50, 100 ng/L) and clean water controls until 8 weeks post-metamorphosis, at which time growth measurements were taken and histopathology assessments were made on gonads, reproductive ducts, liver and kidneys. There were no effects on growth in either study and no signs of overt toxicity, sex reversal or gonad dysgenesis at the concentrations tested. Exposure to tOP caused a treatment-related decrease in circulating thyroxine and an increase in thyroid follicular cell hypertrophy and hyperplasia (25, 50 μg/L). Müllerian duct development was clearly affected following exposure to both chemicals; tOP exposure caused dose-dependent maturation of oviducts in both male and female frogs, whereas TB exposure ca

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.

The effect of diltiazem on the manifestations of hyperthyroidism and thyroid function tests.

PubMed

Keleştimur, F; Aksu, A

1996-01-01

The aim of this study is to evaluate the effect of diltiazem on the symptoms and signs of hyperthyroidism and thyroid function tests and to assess whether diltiazem can be used associated with an anti-thyroid drug, propylthiouracil. Twenty-two patients with hyperthyroidism were included in a prospective, randomized and placebo controlled study. Group 1 (n:12) patients received diltiazem, 60 mg twice a day, for 30 days. Group 2 (n:10) patients received placebo for 30 days. The patients in both groups were given propylthiouracil, 100 mg three times a day, for the last 20 days of the study period. The patients remained in the hospital during the first 10 days. A standardized hyperthyroid symptom score (HSS) and thyroid function tests including thyroid-stimulating hormone (TSH), free thyroxine (free T4), free triiodothyronine (free T3), total thyroxine (T4) and total triiodothyronine (T3) were evaluated before and after 10 and 30 days of the study period. HSS decreased from 27.80 +/- 4.54 to 22.51 +/- 4.04 after 10 days of diltiazem therapy in Group 1 (p < 0.01). But there was no change in HSS in Group 2 (p > 0.01). No significant changes in thyroid function tests have occurred in both groups after 10 days of treatment. Diltiazem can be used in patients with hyperthyroidism to alleviate adrenergic manifestations. It can also be safely combined with propylthiouracil.

Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation.

PubMed

Baumgartner, Christine; da Costa, Bruno R; Collet, Tinh-Hai; Feller, Martin; Floriani, Carmen; Bauer, Douglas C; Cappola, Anne R; Heckbert, Susan R; Ceresini, Graziano; Gussekloo, Jacobijn; den Elzen, Wendy P J; Peeters, Robin P; Luben, Robert; Völzke, Henry; Dörr, Marcus; Walsh, John P; Bremner, Alexandra; Iacoviello, Massimo; Macfarlane, Peter; Heeringa, Jan; Stott, David J; Westendorp, Rudi G J; Khaw, Kay-Tee; Magnani, Jared W; Aujesky, Drahomir; Rodondi, Nicolas

2017-11-28

Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF. We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF. Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4; P for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease. In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF. © 2017 American Heart Association, Inc.

DEVELOPMENTAL DISRUPTION OF THYROID HORMONE: CORRELATIONS WITH HEARING DYSFUNCTION IN RATS.

EPA Science Inventory

A manuscript presents evidence that thyroxine (T4) is a good biomarker-of-effect for developmental neurotoxicity associated with exposure to environmental thyrotoxicants. A major uncertainty in assessing the risks of developmental exposure to thyrotoxicants is the lack of a clear...

MIXTURES OF THYROID DISRUPTING CHEMICALS: TESTING ADDITIVITY OF HEPATIC INDUCERS AND THYROID PEROXIDASE INHIBITORS.

EPA Science Inventory

Humans are exposed to chemical mixtures via diet, occupation, and the environment. Previous data demonstrated that low doses of polycyclic halogenated aromatic hydrocarbons (PHAHs) acting through similar mechanisms result in an additive reduction of thyroxine (T4). If xenobioti...

Thyroid effects of iodine and iodide in potable water

NASA Technical Reports Server (NTRS)

Bull, Richard J.; Thrall, Karla D.; Sherer, Todd T.

1991-01-01

Experiments are reviewed which examine the comparative toxicological effects of iodide (I) and iodine (I2) when used to disinfect drinking water. References are made to a subchronic study in rats, a comparison of the distribution of radiolabeled I and I2, and a demonstration of thyroxine formation in the gastrointestinal tract. The results of the study of the rats are examined in detail; the findings show that I and I2 have opposite effects on the concentrations of thyroid hormones in blood. Iodide slightly decreases circulating thyroxine, while I2 significantly increases the thyroxine concentrations, decreases triiodothyronine levels, and does not change the weight of the thyroid gland. The related effects of I2 ingestion are set forth in detail and are shown to be unique to I2 contamination. Iodine can counteract the effects of iodide and should therefore be used as a disinfectant in drinking water.

Triiodothyronine and thyroxine in urine. II. Renal handling, and effect of urinary protein.

PubMed

Burke, C W; Shakespear, R A

1976-03-01

Mean urinary clearances of T3 were 164 ml/min in normal subjects, 177 in pregnancy, 221 in thyrotoxicosis, 174 in hypothyroidism, and 194 in 3 persons with undetectable T4 but normal T3 levels. T4 clearances were 38 ml/min in normal subjects, 48 in thyrotoxicosis, and 138 in hypothyroidism. Low creatinine clearance was associated with low clearances of T4 and T3. The data suggest urinary excretion of T3 by glomerular filtration of serum unbound T3 with added tubular excretion; and T4 excretion by glomerular filtration of unbound T4 and tubular reabsorption. However, 3-9% of urinary T3 and 5-12% of urinary T4 were bound to urinary proteins, and increased protein excretion caused markedly increased T4 excretion. In addition, 52% of urinary T3 and 68% of urinary T4 were bound to other substances of approximate mol wt 500-2,000, which may influence tubular handling of T3 or T4.

Thyroid-stimulating hormone and free thyroxine levels in persons with HFE C282Y homozygosity, a common hemochromatosis genotype: the HEIRS study.

PubMed

Barton, James C; Leiendecker-Foster, Catherine; Reboussin, David M; Adams, Paul C; Acton, Ronald T; Eckfeldt, John H

2008-08-01

Relationships of thyroid and iron measures in large cohorts are unreported. We evaluated thyroid-stimulating hormone (TSH) and free thyroxine (T4) in white participants of the primary care-based Hemochromatosis and Iron Overload Screening (HEIRS) Study. We measured serum TSH and free T4 in 176 HFE C282Y homozygotes without previous hemochromatosis diagnoses and in 312 controls without HFE C282Y or H63D who had normal serum iron measures and were matched to C282Y homozygotes for Field Center, age group, and initial screening date. We defined hypothyroidism as having TSH >5.00 mIU/L and free T4 <0.70 ng/dL, and hyperthyroidism as having TSH <0.400 mIU/L and free T4 >1.85 ng/dL. Multivariate analyses were performed using age, sex, Field Center, log(10) serum ferritin (SF), HFE genotype, log(10) TSH, and log(10) free T4. Prevalences of hypothyroidism in C282Y homozygotes and controls were 1.7% and 1.3%, respectively, and of hyperthyroidism 0% and 1.0%, respectively. Corresponding prevalences did not differ significantly. Correlations of log(10) SF with log(10) free T4 were positive (p = 0.2368, C282Y homozygotes; p = 0.0492, controls). Independent predictors of log(10) free T4 were log(10) TSH (negative association) and age (positive association); positive predictors of log(10) SF were age, male sex, and C282Y homozygosity. Proportions of C282Y homozygotes and controls who took medications to supplement or suppress thyroid function did not differ significantly. Prevalences of hypothyroidism and hyperthyroidism are similar in C282Y homozygotes without previous hemochromatosis diagnoses and controls. In controls, there is a significant positive association of SF with free T4. We conclude that there is no rationale for routine measurement of TSH or free T4 levels in hemochromatosis or iron overload screening programs.

Gestational exposure to high perchlorate concentrations in drinking water and neonatal thyroxine levels.

PubMed

Amitai, Yona; Winston, Gary; Sack, Joseph; Wasser, Janice; Lewis, Matthew; Blount, Benjamin C; Valentin-Blasini, Liza; Fisher, Nirah; Israeli, Avi; Leventhal, Alex

2007-09-01

To assess the effect of gestational perchlorate exposure through drinking water on neonatal thyroxine (T(4)). T(4) values were compared among newborns in Ramat Hasharon, Israel, whose mothers resided in suburbs where drinking water contained perchlorate < or = 340 microg/L (very high exposure, n = 97), 42-94 microg/L (high exposure, n = 216), and < 3 microg/L (low exposure, n = 843). In the very high and high exposure areas, T(4) values in newborns whose mothers drank tap water exclusively (as determined by a telephone interview) were analyzed as a subset. Serum perchlorate levels in blood from donors residing in the area were used as proxy indicators of exposure. Neonatal T(4) values (mean +/- SD) in the very high, high, and low exposure groups were 13.9 +/- 3.8, 13.9 +/- 3.4, and 14.0 +/- 3.5 microg/dL, respectively (p = NS). Serum perchlorate concentrations in blood from donors residing in areas corresponding to these groups were 5.99 +/- 3.89, 1.19 +/- 1.37, and 0.44 +/- 0.55 microg/L, respectively. T(4) levels of neonates with putative gestational exposure to perchlorate in drinking water were not statistically different from controls. This study finds no change in neonatal T(4) levels despite maternal consumption of drinking water that contains perchlorate at levels in excess of the Environmental Protection Agency (EPA) drinking water equivalent level (24.5 microg/L) based on the National Research Council reference dose (RfD) [0.7 microg/(kg.day)]. Therefore the perchlorate RfD is likely to be protective of thyroid function in neonates of mothers with adequate iodide intake.

Association between l-thyroxine treatment, GH deficiency, and radiological vertebral fractures in patients with adult-onset hypopituitarism.

PubMed

Mazziotti, G; Mormando, M; Cristiano, A; Bianchi, A; Porcelli, T; Giampietro, A; Maffezzoni, F; Serra, V; De Marinis, L; Giustina, A

2014-06-01

In this study, we aimed at evaluating the association between radiological vertebral fractures and levo-thyroxine (l-T4) replacement doses in adult patients with hypopituitarism. Cross-sectional study. We studied 74 adult hypopituitary patients (males, 43; females, 31; mean age, 57 years; and range, 23-79) with central hypothyroidism treated with l-T4 (median daily dose: 1.1  μg/kg). All patients also had severe GH deficiency (GHD) and 38 of them were replaced with recombinant GH. Vertebral fractures were assessed by a quantitative morphometric analysis performed on thoracic and lumbar spine lateral X-ray. Radiological vertebral fractures were found in 23 patients (31.1%) in association with untreated GHD (P=0.02), higher serum free T4 levels (P=0.03), a higher daily dose of l-T4 (P=0.005), and a longer duration of hypopituitarism (P=0.05). When GHD was treated, the prevalence of vertebral fractures was more frequent (P=0.03) in patients receiving high l-T4 doses (third tertile: >1.35  μg/kg per day) as compared with patients who were treated with lower drug doses (first tertile: <0.93  μg/kg per day). Such a difference was not observed in patients with untreated GHD who showed a higher prevalence of vertebral fractures regardless of l-T4 daily doses. Multivariate analysis showed that untreated GHD (odds ratio: 4.27, 95% CI 1.27-14.33; P=0.01) and the daily dose of l-T4 (odds ratio: 4.01, 95% CI 1.16-14.39; P=0.03) maintained a significant and independent association with vertebral fractures in patients with central hypothyroidism. Our data suggest for the first time that a relative overtreatment with l-T4 may influence the fracture risk in some patients with hypopituitarism. © 2014 European Society of Endocrinology.

Graves' disease: an analysis of thyroid hormone levels and hyperthyroid signs and symptoms.

PubMed

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

1989-11-01

Assessment of disease severity for patients with hyperthyroidism involves clinical evaluation and laboratory testing. To determine if there is a correlation between symptoms and thyroid function test results, we prospectively studied hyperthyroid patients using a standardized symptom rating scale and serum thyroid function parameters. We examined 25 patients with untreated, newly diagnosed Graves' disease using the Hyperthyroid Symptom Scale (HSS) and serum levels of thyroxine (T4), triiodothyronine (T3) relative insulin area (RIA), and estimates of free thyroxine index (FTI). In addition, we compared thyroid hormone levels with standard measures of depression and anxiety in these patients. When regression analyses controlling for age were performed, none of these symptom ratings were associated with FTI or T3 RIA. The HSS was correlated with goiter size and anxiety ratings and was inversely correlated with age. The present study suggests that there is no relationship between the clinical assessment of disease severity and serum levels of thyroid hormone in untreated Graves' disease.

Thyroxine administration prevents matrilineal intergenerational consequences of in utero ethanol exposure in rats

PubMed Central

Tunc-Ozcan, Elif; Harper, Kathryn M.; Graf, Evan N.; Redei, Eva E.

2016-01-01

The neurodevelopmental fetal alcohol spectrum disorder (FASD) is characterized by cognitive and behavioral deficits in the offspring. Conferring the deficits to the next generation would increase overall FASD disease burden and prevention of this transmission could be highly significant. Prior studies showed the reversal of these behavioral deficits by low dose thyroxine (T4) supplementation to the ethanol-consuming mothers. Here we aim to identify whether prenatal ethanol (PE) exposure impairs hippocampus-dependent learning and memory in the second-generation (F2) progeny, and whether T4 administration to the ethanol-consuming dam can prevent it. Sprague-Dawley (S) dams received control diets (ad libitum and nutritional control) or ethanol containing liquid diet with and without simultaneous T4 (0.3mg/l diet) administration. Their offspring (SS F1) were mated with naïve Brown Norway (B) males and females generating the SB F2 and BS F2 progeny. Hippocampus-dependent contextual fear memory and hippocampal expression of the thyroid hormone-regulated type 3 deiodinase, (Dio3) and neurogranin (Nrgn) were assessed. SS F1 PE-exposed females and their SB F2 progeny exhibited fear memory deficits. T4 administration to the mothers of F1 females reversed these deficits. Although SS F1 PE-exposed males also experienced fear memory deficit, this was neither transmitted to their BS F2 offspring nor reversed by prenatal T4 treatment. Hippocampal Dio3 and Nrgn expression showed similar pattern of changes. Grandmaternal ethanol consumption during pregnancy affects fear memory of the matrilineal second-generation progeny. Low dose T4 supplementation prevents this process likely via altering allele-specific and total expression of Dio3 in the hippocampus. PMID:27090562

Split high-dose oral levothyroxine treatment as a successful therapy option in myxedema coma.

PubMed

Charoensri, Suranut; Sriphrapradang, Chutintorn; Nimitphong, Hataikarn

2017-10-01

High-dose intravenous thyroxine (T4) is the preferable treatment for myxedema coma. We describe the clinical course of a 69-year-old man who presented with myxedema coma and received oral levothyroxine (LT4) therapy (1 mg) in a split dose. This suggests split high-dose oral LT4 as a therapeutic option in myxedema coma.

CIRCULATING CONCENTRATIONS OF THYROID HORMONE IN BELUGA WHALES (DELPHINAPTERUS LEUCAS): INFLUENCE OF AGE, SEX, AND SEASON.

PubMed

Flower, Jennifer E; Allender, Matthew C; Giovanelli, Richard P; Summers, Sandra D; Spoon, Tracey R; St Leger, Judy A; Goertz, Caroline E C; Dunn, J Lawrence; Romano, Tracy A; Hobbs, Roderick C; Tuttle, Allison D

2015-09-01

Thyroid hormones play a critical physiologic role in regulating protein synthesis, growth, and metabolism. To date, because no published compilation of baseline values for thyroid hormones in beluga whales (Delphinapterus leucas) exists, assessment of thyroid hormone concentrations in this species has been underused in clinical settings. The purpose of this study was to document the concentrations of total thyroxine (tT4) and total triiodothyronine (tT3) in healthy aquarium-maintained and free-ranging beluga whales and to determine the influence of age, sex, and season on the thyroid hormone concentrations. Archived serum samples were collected from healthy aquarium-maintained (n=43) and free-ranging (n=39) belugas, and serum tT4 and tT3 were measured using chemiluminescence immunoassay. The mean tT4 concentration in aquarium-maintained belugas was 5.67±1.43 μg/dl and the mean tT3 concentration was 70.72±2.37 ng/dl. Sex comparisons showed that aquarium-maintained males had significantly greater tT4 and tT3 (9.70±4.48 μg/dl and 92.65±30.55 ng/dl, respectively) than females (7.18±2.82 μg/dl and 77.95±20.37 ng/dl) (P=0.004 and P=0.013). Age comparisons showed that aquarium-maintained whales aged 1-5 yr had the highest concentrations of tT4 and tT3 (8.17±0.17 μg/dl and 105.46±1.98 ng/dl, respectively) (P=0.002 and P<0.001). tT4 concentrations differed significantly between seasons, with concentrations in winter (4.59±1.09 μg/dl) being significantly decreased compared with spring (P=0.009), summer (P<0.0001), and fall (P<0.0001) concentrations. There was a significant difference in tT4 and tT3 concentrations between aquarium-maintained whales (5.67±1.43 μg/dl and 70.72±15.57 ng/dl, respectively) and free-ranging whales (11.71±3.36 μg/dl and 103.38±26.45 ng/dl) (P<0.0001 and P<0.001). Clinicians should consider biologic and environmental influences (age, sex, and season) for a more accurate interpretation of thyroid hormone concentrations in belugas. The findings of this study provide a baseline for thyroid health monitoring and comprehensive health assessments in both aquarium-maintained and free-ranging beluga whales.

The use of konjac glucomannan to lower serum thyroid hormones in hyperthyroidism.

PubMed

Azezli, Adil Dogan; Bayraktaroglu, Taner; Orhan, Yusuf

2007-12-01

Patients with hyperthyroidism occasionally need rapid restoration to the euthyroid state. In view of the increased enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) in thyrotoxicosis, and metabolic effects of konjac glucomannan in gastrointestinal system, we aimed to determine the activity of glucomannan in treatment of hyperthyroidism. A prospective, randomized, placebo-controlled, one-blind study design was used with newly diagnosed 48 hyperthyroid patients (30 patients with Graves' disease and 12 with multinodulary goitre). They were assigned to one of the following treatment groups: I) methimazole 2 x 10 mg, propranolol 2 x 20 mg, and glucomannan (Propol) 2 x 1.3 gr daily for two months; II) methimazole 2 x 10 mg, propranolol 2 x 20 mg, and placebo powder daily for two months. No differences were detected from the point of view of the baseline thyroid hormone levels between groups (p > 0.05). Further analyses revealed that the patients receiving glucomannan at the end of the second, fourth and sixth weeks of the study had significantly lower serum T3, T4, FT3 and FT4 levels than the patients who received placebo (p < 0.05). TSH was not different between the two groups at any specific time (p > 0.05). At week 8, thyroid hormone levels were not shown any differences. The glucomannan-treated group had a more rapid decline in all four serum thyroid hormone levels than the placebo-treated group. We believe our preliminary results indicate that glucomannan may be a safe and easily tolerated adjunctive therapeutic agent in the treatment of thyrotoxicosis. This combination therapy seems most effect during first weeks of treatment of a hyperthyroid patient.

Developmental Exposure to Perfluorohexane Sulfonate (PFHxS) Induces Hypothyroxinemia in Rat Dams and Offspring: Examination of Thyroid Gland and Behavior

EPA Science Inventory

The developing mammalian central nervous system is dependent on thyroid hormones (TH) to control neurogenesis, differentiation and migration. In humans, low maternal serum thyroxine (T4) levels have been correlated to impaired child brain development. Perfluorinated chemicals are...

[Myxedema coma as a rare differential diagnosis of severe consciousness disturbance].

PubMed

Kollmar, R; Schellinger, P D; Bardutzky, J; Meisel, F; Schwaninger, M

2002-12-01

Myxedema coma is a rare and life-threatening complication of untreated hypothyroidism. Therefore, it must be part of the differential diagnosis in comatose patients. We report one patient who presented with CO(2) narcosis,hypothermia, bradycardia,hyporeflexia, tetraparesis, ascitis, pleural effusions, and heart insufficiency. Examination of the CSF, cranial CT, MRI, and MR angiography were normal. In suspicion of myxedema coma,the patient was treated with high dose L-thyroxine and hydrocortisone for preventing secondary adrenal insufficiency. A fast clinical recovery, decreased T4 (7.2 ng/l) and T3 (0.93 ng/l), and increased TSH (20.19 mU/l) together with the following anamnesis of radio iodine therapy and insufficient thyroxine intake confirmed the diagnosis. In conclusion, treatment of the myxedema coma must be started as soon as the laboratory results are confirmatory, since its course depends on the time of initiation of treatment.

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

PubMed

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

1990-01-01

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

Hypoplastic anaemia complicating myxoedema coma.

PubMed

Song, S H; McCallum, C J; Campbell, I W

1998-10-01

The case of a 68 year old women presenting in myxoedema coma is described. She was found to be anaemic with a haemoglobin of 8.2 g/dl. Further investigations showed a pancytopenia and a hypoplastic anaemia confirmed by bone marrow. The patient recovered and became euthyroid following initial treatment with intravenous tri-iodothyronine (T3) and later oral thyroxine (T4) replacement with resolution of pancytopenia and return of bone marrow to normal.

Substitution of Liothyronine at a 1:5 Ratio for a Portion of Levothyroxine: Effect on Fatigue, Symptoms of Depression, and Working Memory Versus Treatment with Levothyroxine Alone

PubMed Central

Rodriguez, Tom; Lavis, Victor R.; Meininger, Janet Ck.; Kapadia, Asha S.; Stafford, Linda F.

2006-01-01

Background This study was planned at a time when important questions were being raised about the adequacy of using one hormone to treat hypothyroidism instead of two. Methods This trial attempted to replicate prior findings which suggested that substituting 12.5 μg of liothyronine for 50 μg of levothyroxine might improve mood, cognition, and physical symptoms in patients with primary hypothyroidism. Additionally, this trial aimed to extend the above findings to fatigue and to assess for differential effects in subjects with low and high fatigue at baseline. A randomized, double-blind, two-period, crossover design was used. Thirty subjects stabilized on levothyroxine (L-T4) at an endocrinology and diabetes clinic were recruited. Sequence one received their standard L-T4 dose in one capsule and placebo in another. Sequence two received their usual L-T4 dose minus 50 μg in one capsule and 10 μg of liothyronine (L-T3) in the other. At the end of the first six weeks, subjects were crossed over. T tests were used to assess carry-over and treatment effects. Results Twenty-seven subjects completed the trial. Mean L-T4 dose was 121 μg/d (± 26.0) at baseline. There were no significant differences in fatigue and symptoms of depression between treatments. Measures of working memory were unchanged. While on substitution treatment, free thyroxine index was reduced by 0.7 (p<0.001), total serum thyroxine was reduced by 3.0 μg/dl (p<0.001), and total serum triiodothyronine was increased by 20.5 ng/dl (p=0.004). Conclusions With regard to the outcomes measured, substitution of L-T3 at a 1:5 ratio for a portion of baseline L-T4 was no better than treatment with the original dose of L-T4 alone. PMID:16006298

Relationship Between Circulating Thyroid-Stimulating Hormone, Free Thyroxine, and Free Triiodothyronine Concentrations and 9-Year Mortality in Euthyroid Elderly Adults.

PubMed

Ceresini, Graziano; Marina, Michela; Lauretani, Fulvio; Maggio, Marcello; Bandinelli, Stefania; Ceda, Gian P; Ferrucci, Luigi

2016-03-01

To determine the association between plasma thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels and all-cause mortality in older adults who had levels of all three hormones in the normal range. Longitudinal. Community-based. Euthyroid Invecchiare in Chianti study participants aged 65 and older (N = 815). Plasma TSH, FT3, and FT4 levels were predictors, and 9-year all-cause mortality was the outcome. Cox proportional hazards models adjusted for confounders were used to examine the relationship between TSH, FT3, and FT4 quartiles and all-cause mortality over 9 years of follow-up. During follow-up (mean person-years 8,643.7, range 35.4-16,985.0), 181 deaths occurred (22.2%). Participants with TSH in the lowest quartile had higher mortality than the rest of the population. After adjusting for multiple confounders, participants with TSH in the lowest quartile (hazard ratio = 2.22, 95% confidence interval = 1.19-4.22) had significantly higher all-cause mortality than those with TSH in the highest quartile. Neither FT3 nor FT4 was associated with mortality. In elderly euthyroid subjects, normal-low TSH is an independent risk factor for all-cause mortality. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

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.

Simulation of Post-Thyroidectomy Treatment Alternatives for Triiodothyronine or Thyroxine Replacement in Pediatric Thyroid Cancer Patients

PubMed Central

Ben-Shachar, Rotem; Huang, Stephen A.; DiStefano, Joseph J.

2012-01-01

Background As in adults, thyroidectomy in pediatric patients with differentiated thyroid cancer is often followed by 131I remnant ablation. A standard protocol is to give normalizing oral thyroxine (T4) or triiodothyronine (T3) after surgery and then withdraw it for 2 to 6 weeks. Thyroid remnants or metastases are treated most effectively when serum thyrotropin (TSH) is high, but prolonged withdrawals should be avoided to minimize hypothyroid morbidity. Methods A published feedback control system model of adult human thyroid hormone regulation was modified for children using pediatric T4 kinetic data. The child model was developed from data for patients ranging from 3 to 9 years old. We simulated a range of T4 and T3 replacement protocols for children, exploring alternative regimens for minimizing the withdrawal period, while maintaining normal or suppressed TSH during replacement. The results are presented with the intent of providing a quantitative basis to guide further studies of pediatric treatment options. Replacement was simulated for up to 3 weeks post-thyroidectomy, followed by various withdrawal periods. T4 vs. T3 replacement, remnant size, dose size, and dose frequency were tested for effects on the time for TSH to reach 25 mU/L (withdrawal period). Results For both T3 and T4 replacement, higher doses were associated with longer withdrawal periods. T3 replacement yielded shorter withdrawal periods than T4 replacement (up to 3.5 days versus 7–10 days). Higher than normal serum T3 concentrations were required to normalize or suppress TSH during T3 monotherapy, but not T4 monotherapy. Larger remnant sizes resulted in longer withdrawal periods if T4 replacement was used, but had little effect for T3 replacement. Conclusions T3 replacement yielded withdrawal periods about half those for T4 replacement. Higher than normal hormone levels under T3 monotherapy can be partially alleviated by more frequent, smaller doses (e.g., twice a day). LT4 may be the preferred option for most children, given the convenience of single daily dosing and familiarity of pediatric endocrinologists with its administration. Remnant effects on withdrawal period highlight the importance of minimizing remnant size. PMID:22578300

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.

Feline focus: Diagnostic testing for feline thyroid disease: hyperthyroidism.

PubMed

Peterson, Mark E

2013-08-01

In older cats presenting with clinical features of hyperthyroidism, confirming the diagnosis of thyroid disease is usually straightforward. However, the potential for false-negative and false-positive results exists with all thyroid function tests, especially when used for routine screening of large numbers of asymptomatic cats. Therefore, all thyroid function test results must be interpreted in light of the cat's history, clinical signs, and other laboratory findings. If a high serum thyroxine (T4) value is found in a cat that lacks clinical signs of hyperthyroidism, or if hyperthyroidism is suspected in a cat with normal total T4 concentrations, repeating the total T4 analysis, determining the free T4 concentration, or performing thyroid scintigraphy may be needed to confirm the diagnosis.

Circulating CXCR5+CD4+ T cells participate in the IgE accumulation in allergic asthma.

PubMed

Gong, Fang; Zhu, Hua-Yan; Zhu, Jie; Dong, Qiao-Jing; Huang, Xuan; Jiang, Dong-Jin

2018-05-01

The pathogenesis of allergic asthma is primarily characterized by abnormality in immunoglobin(Ig)E pathway, suggesting a possible role for follicular helper T cells (Tfh) in the genesis of excessive IgE accumulation. The blood chemokine (C-X-C motif) receptor 5 (CXCR)5 + CD4 + T cells, known as "circulating" Tfh, share common functional characteristics with Tfh cells from germinal centers. The aim of this study was to determine the phenotypes and functions of circulating CXCR5 + CD4 + T cells in allergic asthmatics. Here we found the frequency of the circulating CXCR5 + CD4 + T cells was raised in allergic asthma compared with healthy control (HC). Phenotypic assays showed that activated circulating CXCR5 + CD4 + T cells display the key features of Tfh cells, including invariably coexpressed programmed cell death (PD)-1 and inducible costimulator (ICOS). The frequency of interleukin IL-4 + -, IL-21 + -producing CXCR5 + CD4 + T cells was increased in allergic asthma patients compared with HC. Furthermore, sorted circulating CXCR5 + CD4 + T cells from allergic asthma patients boosted IgE production in coculture assay which could be inhibited by IL-4 or IL-21 blockage. Interestingly, IL-4 + -, IL-21 + -CXCR5 + CD4 + T cells positively correlated with total IgE in the blood. Our data indicated that circulating CXCR5 + CD4 + T cells may have a significant role in facilitating IgE production in allergic asthma patients. Copyright © 2018 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

A DFT investigation of a bulky biomimetic model catalyzing the 5'-outer ring deiodination of thyroxine.

PubMed

Fortino, Mariagrazia; Marino, Tiziana; Russo, Nino; Sicilia, Emilia

2016-12-01

This paper illustrates the outcomes of a density functional theory investigation aimed at unraveling mechanistic aspects of the 5'-outer ring deiodination process of thyroxine (T4) assisted by the sterically protected organoselenol compound BpqSeH. BpqSeH, which was previously synthesized and tested for its deiodinase activity, is able to afford the active hormone 3,5,3'-tetraiodothyronine (T3) by selective outer-ring deiodination of T4, and to protect the SeH moiety inside the nano-sized molecular cavity from further reactivity, allowing its isolation and characterization. Calculations were also performed including an imidazole ring that, mimicking a His residue in the active site of the original enzyme, plays an crucial role in deprotonating the selenol moiety. Both the suggested enol/keto tautomerization and the previously proven formation of an intermediate whose main characteristic is the presence of a Se⋯I⋯C halogen bond, were examined along the pathway leading to 5'-outer ring deiodination. The calculated potential energy surface showed that neither the pathway encompassing enol/keto tautomerism nor the formation of a halogen bond paving the way to C-I bond breaking and chalcogen-I bond forming is viable. The exergonic formation of the final selenenyl iodide product confirms the stabilization effect of the molecular cavity. Graphical Abstract Computed free energy profile describing the 5'-outer deiodination of thyroxine assisted by the steric hindered organoselenol BpqSH compound. The molecular electrostatic potential map reoported for the INT1 intermediate shows the non-covalent Se-I interaction, due to the attraction between charges of opposite sign, that weakens the C-I bond and prepares the formation of the new Se-I bond.

Prevalence of and risk factors for feline hyperthyroidism in South Africa.

PubMed

McLean, Joanne L; Lobetti, Remo G; Mooney, Carmel T; Thompson, Peter N; Schoeman, Johan P

2017-10-01

Objectives Hyperthyroidism is a disorder of older cats that may have a geographical variation in prevalence. Prevalence studies have not yet been performed in South Africa, a geographical area where hyperthyroidism in cats has recently been observed and where, reportedly, the incidence appears to be increasing. The purpose of this study was to determine the prevalence of feline hyperthyroidism in South Africa and to identify any potential risk factors. Further information on the worldwide prevalence and possible causative factors would increase our understanding of the aetiology of this disease and help identify any preventive measures. Methods Serum total thyroxine (tT4) and canine thyroid-stimulating hormone (cTSH) were measured in 302 cats aged 9 years and older that were presented at various veterinary clinics throughout South Africa. In cats with equivocal tT4 and undetectable cTSH values, serum free thyroxine (fT4) was also measured. At the time of blood sampling a questionnaire was completed regarding vaccination history, internal and external parasite control, diet and environment. Results Prevalence of hyperthyroidism (tT4 >50 nmol/l or tT4 between 30 and 50 nmol/l with TSH <0.03 ng/ml and fT4 >50 pmol/l) was 7% (95% confidence interval 4.4-10.4), with no significant difference between healthy (5%) and sick (8%) cats. Cats ⩾12 years of age (odds ratio [OR] 4.3, P = 0.02) and cats eating canned food (OR 2.1, P = 0.1) were more likely to be diagnosed with hyperthyroidism. No significant relationship between vaccinations, parasite control or indoor environment and hyperthyroidism was observed. Hyperthyroid cats were more likely to present with weight loss (OR 3.2, P = 0.01) and with a heart rate ⩾200 beats per min (OR 5, P = 0.01) than cats without the disease. Conclusions and relevance Hyperthyroidism does not appear to be uncommon in the South African cat population. Risk factors for hyperthyroidism, specifically older age and eating canned food, were present in this as in other reported populations.

Amphibians and ultra high diluted thyroxine--further experiments and re-analysis of data.

PubMed

Endler, Peter Christian; Scherer-Pongratz, Waltraud; Harrer, Bernhard; Lingg, Gerhard; Lothaller, Harald

2015-10-01

A model of thyroxine and metamorphosis of highland amphibians is frequently mentioned as an example of experiments on extremely diluted substances in discussions around 'homeopathy'. The model was scrutinized by reanalysing the results of the initial researcher A and a second researcher B as well as of 5 external researchers C between 1990 and 2013. Rana temporaria larvae were taken from an alpine highland biotope. The test solution was thyroxine 10(-30) (T30x), tetra-iodo-thyronine sodium pentahydrate diluted with pure water in 26 steps of 1:10, being agitated after each step. Analogously prepared water (W30x) was used for control. Tadpoles were observed from the 2-legged to the 4-legged stage. Experiments were performed in different years, at different times of season, and their duration could vary. Frequencies of 4-legged animals, effect sizes and areas under the curves (AUCs) were calculated and regression analyses were performed to investigate possible correlations between year, season, duration etc. Experiments were in line with animal protection guidelines. The total set of data A + B + C as well as subsets A (initial researcher, N=286+293), B (second centre, 965 + 965) and C (5 external researchers, 690 + 690) showed an effect of extremely diluted agitated thyroxine reverse to that known of molecular thyroxin, i.e. test values were below control by 11.4% for A, 9.5% for B and 7.0% for C (p<0.001 for each of the subsets). The effect size (Cohen's d) was >0.8 (large) for both A and B and 0.74 (medium) for C. Although a perfect reproducibility was not obtained, this paradoxical phenomenon was generally consistent in different observations. Correlations were found between details of laboratory handling, as well as environment temperature, and the size of the results. Copyright © 2015 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Relationship Between the Thyroid Axis and Alcohol Craving

PubMed Central

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

2015-01-01

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

Assessment of thyroid function in dogs with low plasma thyroxine concentration.

PubMed

Diaz Espineira, M M; Mol, J A; Peeters, M E; Pollak, Y W E A; Iversen, L; van Dijk, J E; Rijnberk, A; Kooistra, H S

2007-01-01

Differentiation between hypothyroidism and nonthyroidal illness in dogs poses specific problems, because plasma total thyroxine (TT4) concentrations are often low in nonthyroidal illness, and plasma thyroid stimulating hormone (TSH) concentrations are frequently not high in primary hypothyroidism. The serum concentrations of the common basal biochemical variables (TT4, freeT4 [fT4], and TSH) overlap between dogs with hypothyroidism and dogs with nonthyroidal illness, but, with stimulation tests and quantitative measurement of thyroidal 99mTcO4(-) uptake, differentiation will be possible. In 30 dogs with low plasma TT4 concentration, the final diagnosis was based upon histopathologic examination of thyroid tissue obtained by biopsy. Fourteen dogs had primary hypothyroidism, and 13 dogs had nonthyroidal illness. Two dogs had secondary hypothyroidism, and 1 dog had metastatic thyroid cancer. The diagnostic value was assessed for (1) plasma concentrations of TT4, fT4, and TSH; (2) TSH-stimulation test; (3) plasma TSH concentration after stimulation with TSH-releasing hormone (TRH); (4) occurrence of thyroglobulin antibodies (TgAbs); and (5) thyroidal 99mTcO4(-) uptake. Plasma concentrations of TT4, fT4, TSH, and the hormone pairs TT4/TSH and fT4/TSH overlapped in the 2 groups, whereas, with TgAbs, there was 1 false-negative result. Results of the TSH- and TRH-stimulation tests did not meet earlier established diagnostic criteria, overlapped, or both. With a quantitative measurement of thyroidal 99mTcO4(-) uptake, there was no overlap between dogs with primary hypothyroidism and dogs with nonthyroidal illness. The results of this study confirm earlier observations that, in dogs, accurate biochemical diagnosis of primary hypothyroidism poses specific problems. Previous studies, in which the TSH-stimulation test was used as the "gold standard" for the diagnosis of hypothyroidism may have suffered from misclassification. Quantitative measurement of thyroidal 99mTcO- uptake has the highest discriminatory power with regard to the differentiation between primary hypothyroidism and nonthyroidal illness.

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

PubMed

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

2014-08-01

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

Increased anxiety and fear memory in adult mice lacking type 2 deiodinase.

PubMed

Bárez-López, Soledad; Montero-Pedrazuela, Ana; Bosch-García, Daniel; Venero, César; Guadaño-Ferraz, Ana

2017-10-01

A euthyroid state in the brain is crucial for its adequate development and function. Impairments in thyroid hormones (THs; T3 or 3,5,3'-triiodothyronine and T4 or thyroxine) levels and availability in brain can lead to neurological alterations and to psychiatric disorders, particularly mood disorders. The thyroid gland synthetizes mainly T4, which is secreted to circulating blood, however, most actions of THs are mediated by T3, the transcriptionally active form. In the brain, intracellular concentrations of T3 are modulated by the activity of type 2 (D2) and type 3 (D3) deiodinases. In the present work, we evaluated learning and memory capabilities and anxiety-like behavior at adult stages in mice lacking D2 (D2KO) and we analyzed the impact of D2-deficiency on TH content and on the expression of T3-dependent genes in the amygdala and the hippocampus. We found that D2KO mice do not present impairments in spatial learning and memory, but they display emotional alterations with increased anxiety-like behavior as well as enhanced auditory-cued fear memory and spontaneous recovery of fear memory following extinction. D2KO mice also presented reduced T3 content in the hippocampus and decreased expression of the T3-dependent gene Dio3 in the amygdala suggesting a hypothyroid status in this structure. We propose that the emotional dysfunctions found in D2KO mice can arise from the reduced T3 content in their brain, which consequently leads to alterations in gene expression with functional consequences. We found a downregulation in the gene encoding for the calcium-binding protein calretinin (Calb2) in the amygdala of D2KO mice that could affect the GABAergic transmission. The current findings in D2KO mice can provide insight into emotional disorders present in humans with DIO2 polymorphisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

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 ...

Structural and functional maturation of rat gastrointestinal barrier with thyroxine

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

Israel, E.J.; Pang, K.Y.; Harmatz, P.R.

It has been noted that the closure of the intestinal barrier to immunoglobulins is a normal maturational process in the rat. It has also been noted that the microvillus membrane (MVM) of newborn animals differs from adult MVM. The purpose of this study is to document whether thyroid hormone can induce closure in vivo in the rat and to relate this effect of thyroxine to the structural and functional maturation of the intestinal MVM. To assess closure, 2-wk-old rats were fed in rat immunoglobulin G (IgG), and serum antibody binding activity was measured 4 h later. The antibody binding activitymore » of treated animals (T) was 1.5-2 times less than that of controls (C), indicating that thyroxine stimulates closure. The MVM similarly showed signs of maturation. Structural maturation was demonstrated by the lower fluidity of the thyroid-treated animals' membranes. Under the influence of thyroxine, the number of receptors on the MVM for IgG had decreased, while the K/sub a/ remained the same, demonstrating the functional maturation of the MVM. In conclusion, thryoid hormone can induce both structural and functional maturation of the intestinal MVM and can enhance the intestinal mucosal barrier by decreasing the penetration of antibodies.« less

Effects of adult dysthyroidism on the morphology of hippocampal granular cells in rats.

PubMed

Martí-Carbonell, Maria Assumpció; Garau, Adriana; Sala-Roca, Josefina; Balada, Ferran

2012-01-01

Thyroid hormones are essential for normal brain development and very important in the normal functioning of the brain. Thyroid hormones action in the adult brain has not been widely studied. The effects of adult hyperthyroidism are not as well understood as adult hypothyroidism, mainly in hippocampal granular cells. The purpose of the present study is to assess the consequences of adult hormone dysthyroidism (excess/deficiency of TH) on the morphology of dentate granule cells in the hippocampus by performing a quantitative study of dendritic arborizations and dendritic spines using Golgi impregnated material. Hypo-and hyperthyroidism were induced in rats by adding 0.02 percent methimazole and 1 percent L-thyroxine, respectively, to drinking water from 40 days of age. At 89 days, the animals' brains were removed and stained by a modified Golgi method and blood samples were collected in order to measure T4 serum levels. Neurons were selected and drawn using a camera lucida. Our results show that both methimazole and thyroxine treatment affect granule cell morphology. Treatments provoke alterations in the same direction, namely, reduction of certain dendritic-branching parameters that are more evident in the methimazole than in the thyroxine group. We also observe a decrease in spine density in both the methimazole and thyroxine groups.

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).

Plasmapheresis rapidly eliminates thyroid hormones from the circulation, but does not affect the speed of TSH recovery following prolonged suppression.

PubMed

Liel, Yair; Weksler, Natan

2003-01-01

To report an attempt to shorten the preparation interval before radioactive iodine administration using plasmapheresis in a 77-year-old woman with a history of papillary thyroid carcinoma with local recurrence and lung metastases, in whom the administration of a high dose of radioactive iodine was intended as a desperate rescue procedure. The patient was initially started on cholestyramine. Two days later, plasmapheresis was performed. Plasmapheresis rapidly decreased free tri-iodothyronine (FT(3)) and free thyroxine (FT(4)). Serum FT(4) subsequently remained low, while FT(3) recovered the next day. Thyroid-stimulating hormone (TSH) reached 25 mIU/l in 14 days, which is within the time frame required to reach the target TSH level by withdrawing levothyroxine alone. Plasmapheresis is very effective in eliminating thyroid hormones from the circulation. However, it does not seem to accelerate thyrotroph recovery to a considerable extent after prolonged suppression. Copyright 2003 S. Karger AG, Basel

Establishment of reference intervals for serum thyroid-stimulating hormone, free and total thyroxine, and free and total triiodothyronine for the Beckman Coulter DxI-800 analyzers by indirect method using data obtained from Chinese population in Zhejiang Province, China.

PubMed

Wang, Yan; Zhang, Yu-Xia; Zhou, Yong-Lie; Xia, Jun

2017-07-01

In order to establish suitable reference intervals of thyroid-stimulating hormone (TSH), free (unbound) T4 (FT4), free triiodothyronine (FT3), total thyroxine (T4), and total triiodothyronine (T3) for the patients collected in Zhejiang, China, an indirect method was developed using the data from the people presented for routine health check-up. Fifteen thousand nine hundred and fifty-six person's results were reviewed. Box-Cox or Case Rank was used to transform the data to normal distribution. Tukey and Box-Plot methods were used to exclude the outliers. Nonparametric method was used to establish the reference intervals following the EP28-A3c guideline. Pearson correlation was used to evaluate the correlation between hormone levels and age, while Mann-Whitney U test was employed for quantification of concentration differences on the people who are younger and older than 50 years old. Reference intervals were 0.66-4.95 mIU/L (TSH), 8.97-14.71 pmol/L (FT4), 3.75-5.81 pmol/L (FT3), 73.45-138.93 nmol/L (total T4), and 1.24-2.18 nmol/L (total T3) in male; conversely, reference intervals for female were 0.72-5.84 mIU/L (TSH), 8.62-14.35 pmol/L (FT4), 3.59-5.56 pmol/L (FT3), 73.45-138.93 nmol/L (total T4), and 1.20-2.10 nmol/L (total T3). FT4, FT3, and total T3 levels in male and FT4 level in female had an inverse correlation with age. Total T4 and TSH levels in female were directly correlated. Significant differences in these hormones were also found between younger and older than 50 years old except FT3 in female. Indirect method can be applied for establishment of reference intervals for TSH, FT4, FT3, total T4, and total T3. The reference intervals are narrower than those previously established. Age factor should also be considered. © 2016 Wiley Periodicals, Inc.

Investigating endocrine and physiological parameters of captive American kestrels exposed by diet to selected organophosphate flame retardants

USGS Publications Warehouse

Fernie, KJ; Palace, V; Peters, L.; Basu, Niladri; Letcher, R.J.; Karouna-Renier, Natalie K.; Schultz, Sandra; Lazarus, Rebecca S.; Rattner, Barnett A.

2015-01-01

Organophosphate triesters are high production volume additive flame retardants (OPFRs) and plasticizers. Shown to accumulate in abiotic and biotic environmental compartments, little is known about the risks they pose. Captive adult male American kestrels (Falco sparverius) were fed the same dose (22 ng OPFR/g kestrel/d) daily (21 d) of tris(2- butoxyethyl) phosphate (TBOEP), tris(2-chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCIPP), or tris(1,2-dichloro-2-propyl) phosphate (TDCIPP). Concentrations were undetected in tissues (renal, hepatic), suggesting rapid metabolism. There were no changes in glutathione status, indicators of hepatic oxidative status, or the cholinergic system (i.e., cerebrum, plasma cholinesterases; cerebrum muscarinic, nicotinic receptors). Modest changes occurred in hepatocyte integrity and function (clinical chemistry). Significant effects on plasma free triiodothyronine (FT3) concentrations occurred with exposure to TBOEP, TCEP, TCIPP, and TDCIPP; TBOEP and TCEP had additional overall effects on free thyroxine (FT4), whereas TDCIPP also influenced total thyroxine (TT4). Relative increases (32%−96%) in circulating FT3, TT3, FT4, and/or TT4 were variable with each OPFR at 7 d exposure, but limited thereafter, which was likely maintained through decreased thyroid gland activity and increased hepatic deiodinase activity. The observed physiological and endocrine effects occurred at environmentally relevant concentrations and suggest parent OPFRs or metabolites may have been present despite rapid degradation.

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.

Adrenocortical Response to Stress and Thyroid Hormone Status in Free-Living Nestling White Storks (Ciconia ciconia) Exposed to Heavy Metal and Arsenic Contamination

PubMed Central

Baos, Raquel; Blas, Julio; Bortolotti, Gary R.; Marchant, Tracy A.; Hiraldo, Fernando

2006-01-01

Background/Objective Endocrine parameters have proven useful in the detection of early or low-level responses to pollutants. Although most of the studies on endocrine modulation have been focused on processes involving gonadal steroids, contaminants may target other parts of the endocrine system as well. In this study we examined the adrenocortical stress response and thyroid hormone status in free-living nestling white storks (Ciconia ciconia) in relation to heavy metals (zinc, lead, copper, cadmium) and arsenic levels in blood. Methods Fieldwork was conducted in an area polluted by the Aznalcóllar mine accident (southwestern Spain) and in a reference site. We used a standardized capture, handling, and restraint protocol to determine both baseline and maximum plasma corticosterone. Circulating levels of thyroxine (T4) and triiodothyronine (T3) were also measured. Results No effects of metals or As were found on baseline corticosterone, but maximum levels of corticosterone were positively related to Pb in both locations. This relationship was stronger in single nestlings than in birds from multiple-chick broods, which suggests a greater impact of Pb on more stressed individuals. Metal pollution did not affect plasma T4 or T3 levels, although thyroid status differed with location. Conclusions Because a compromised hypothalamus–pituitary–adrenal (HPA) function can have far-reaching consequences in terms of altered behavioral and metabolic processes necessary for survival, our results suggest that birds exposed to sublethal Pb levels may be at risk through an altered adrenocortical stress response, and further support the idea that HPA axis-related end points might be useful indicators of metal exposure and potential toxicity in wild animals. PMID:17035132

Exposure to non-persistent pesticides and thyroid function: A systematic review of epidemiological evidence.

PubMed

Campos, Élida; Freire, Carmen

2016-08-01

Numerous pesticides are recognized for their endocrine-disrupting properties. Non-persistent pesticides such as organophosphates, dithiocarbamates and pyrethroids may interfere with thyroid function as suggested by animal studies. However, the influence of chronic exposure to these compounds on thyroidal functions in humans remains to be determined. The present study aimed to review epidemiological evidence for an association between exposure to non-persistent pesticides and circulating levels of thyroid hormones (thyroxin [T4] and triiodothyronine [T3]) and thyroid-stimulating hormone (TSH). A systematic review was conducted using MEDLINE, SCOPUS and Virtual Health Library (BVS) databases. Articles were limited to original studies and reports published in English, Portuguese or Spanish. Nineteen epidemiological studies were identified, 17 of which were cross-sectional, 14 were of occupationally exposed workers and 11 used exposure biomarkers. Fungicides and organophosphates (OP) insecticides were the most studied pesticides. Although methodological heterogeneity between studies was noted, particularly regarding study design, exposure assessment, and control of confounding, most of them showed associations with changes in T3 and T4, and/or TSH levels, while results from a few of these are consistent with experimental data supporting the findings that non-persistent pesticide exposure exerts hypothyroid-like effects. However, reporting quality was moderate to poor in 50% of the studies, particularly regarding method of selection of participants and discussion of external validity. Overall, current knowledge regarding the impact of non-persistent pesticides on human thyroid function is still limited. Given the widespread use of pesticides, future research should assess effects of exposure to currently-used pesticides in cohort studies combining comprehensive questionnaire-based assessment and biomarkers. Investigators need to pay particular attention to exposure during critical windows of brain development and exposure in agricultural populations. Copyright © 2016 Elsevier GmbH. All rights reserved.

Improvement of left ventricular remodeling after myocardial infarction with eight weeks L-thyroxine treatment in rats.

PubMed

Chen, Yue-Feng; Weltman, Nathan Y; Li, Xiang; Youmans, Steven; Krause, David; Gerdes, Anthony Martin

2013-02-14

Left ventricular (LV) remodeling following large transmural myocardial infarction (MI) remains a pivotal clinical issue despite the advance of medical treatment over the past few decades. Identification of new medications to improve the remodeling process and prevent progression to heart failure after MI is critical. Thyroid hormones (THs) have been shown to improve LV function and remodeling in animals post-MI and in the human setting. However, changes in underlying cellular remodeling resulting from TH treatment are not clear. MI was produced in adult female Sprague-Dawley rats by ligation of the left descending coronary artery. L-thyroxine (T4) pellet (3.3 mg, 60 days sustained release) was used to treat MI rats for 8 weeks. Isolated myocyte shape, arterioles, and collagen deposition in the non-infarcted area were measured at terminal study. T4 treatment improved LV ±dp/dt, normalized TAU, and increased myocyte cross-sectional area without further increasing myocyte length in MI rats. T4 treatment increased the total LV tissue area by 34%, increased the non-infarcted tissue area by 41%, and increased the thickness of non-infarcted area by 36% in MI rats. However, myocyte volume accounted for only ~1/3 of the increase in myocyte mass in the non-infarct area, indicating the presence of more myocytes with treatment. T4 treatment tended to increase the total length of smaller arterioles (5 to 15 μm) proportional to LV weight increase and also decreased collagen deposition in the LV non-infarcted area. A tendency for increased metalloproteinase-2 (MMP-2) expression and tissue inhibitor of metalloproteinases (TIMPs) -1 to -4 expression was also observed in T4 treated MI rats. These results suggest that long-term T4 treatment after MI has beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the non-infarcted area. Most importantly, results suggest improved survival of myocytes in the peri-infarct area.

Relationship Between Circulating Concentrations of Thyrotropin, Free Thyroxine, and Free Triiodothyronine and 9-Year Mortality in Euthyroid Elderly Subjects

PubMed Central

Ceresini, Graziano; Marina, Michela; Lauretani, Fulvio; Maggio, Marcello; Bandinelli, Stefania; Ceda, Gian Paolo; Ferrucci, Luigi

2015-01-01

Objectives Thyroid dysfunction in the elderly is associated with adverse clinical outcomes, with mortality being associated with low TSH. However, it is still unknown whether variability of thyroid function test within the reference range is associated with mortality in older adults. We studied the association between plasma levels of TSH, free T3 (FT3), and free T4 (FT4), and all-cause mortality in older adults who had all three hormones within the normal range. Design Longitudinal study Setting Community-based Participants Total of 815 euthyroid participants of the InCHIANTI study, aged 65 years or older Measurements All subjects had TSH, FT3, and FT4 within the reference range at baseline. Plasma TSH, FT3 and FT4 were predictors and 9-year all-cause mortality was the outcome. Cox proportional hazards models adjusted for confounders were used to examine the relationship between quartiles of TSH, FT3, and FT4 and all-cause mortality over 9 years of follow-up. Results During the follow-up (mean persons-years 8643.74 [min-max, 35.36-16985.00]), 181 deaths occurred (22.2%). Participants with TSH in the lower quartile had higher mortality than the rest of the population. After adjusting for multiple confounders, participants with TSH in the lowest quartile (Hazard Ratio: 2.22; 95% Confidence Interval: 1.19–4.22) had significantly higher all-cause mortality than those with TSH in the highest quartile. Neither FT3 nor FT4 were associated with mortality. Conclusions In euthyroid elderly subjects, normal-low TSH represents an independent risk factor for all-cause mortality. PMID:27000328

Etiological evaluation of primary congenital hypothyroidism cases.

PubMed

Bezen, Diğdem; Dilek, Emine; Torun, Neşe; Tütüncüler, Filiz

2017-06-01

Primary congenital hypothyroidism is frequently seen endocrine disorder and one of the preventable cause of mental retardation. Aim of study was to evaluate the frequency of permanent/transient hypothyrodism, and to detect underlying reason to identfy any marker which carries potential to discriminate permanent/transient form. Forty eight cases older than 3 years of age, diagnosed as primary congenital hypothyroidism and started thyroxin therapy in newborn-period, and followed up between January 2007-June 2013 were included in the study. Thyroid hormon levels were evaluated and thyroid ultrasonography was performed in cases who are at the end of their 3 years of age, after 6 weeks of thyroxine free period. Thyroid sintigraphy was performed if serum thyroid-stimulating hormone was high (≥ 5 mIU/mL) and perchlorate discharge test was performed if uptake was normal or increased on sintigraphy. Cases with thyroid-stimulating hormone levels ≥ 5 mIU/mL were defined as permanent primary congenital hypothyroidism group and as transient primary congenital hypothyroidism group with normal thyroid hormones during 6 months. The mean age was 3.8±0.7 years. Mean diagnosis age was 16.6±6.5 days and 14 cases (29.2%) were diagnosed by screening program of Ministry of Health. There were 23 cases (14F, 9M) in permanent primary congenital hypothyroidism group and 12 (52.2%) of them were dysgenesis (8 hypoplasia, 4 ectopia), and 11 (47.8%) dyshormonogenesis. In transient primary congenital hypothyroidism group, there were 25 cases (17M, 8F). The mean thyroid-stimulating hormone levels at diagnosis were similar in two groups. The mean thyroxin dose in permanent primary congenital hypothyroidism group was significantly higher than transient group at the time of thyroxin cessation (2.1±0.7, 1.5±0.5 mg/kg/d, respectively, p=0.004). Thyroxin dose ≥1.6 mcg/kg/d was 72% sensitive and 69.6% specific for predicting permenant primary congenital hypothyroidism. Transient primary congenital hypothyroidism is more frequent than expected and found often in males in the primary congenital hypothyroidism cases, started thyroxin therapy in neonatal period. While fT4, thyroid-stimulating hormone, Tg levels at diagnosis do not predict transient/permenant primary congenital hypothyroidism, thyroxin dose before the therapy cessation at the age of 3 may make the distinction between transient/permenant primary congenital hypothyroidism.

Exogenous T3 toxicosis following consumption of a contaminated weight loss supplement.

PubMed

D'Arcy, R; McDonnell, M; Spence, K; Courtney, C H

2017-01-01

A 42-year-old male presented with a one-week history of palpitations and sweating episodes. The only significant history was of longstanding idiopathic dilated cardiomyopathy. Initial ECG demonstrated a sinus tachycardia. Thyroid function testing, undertaken as part of the diagnostic workup, revealed an un-measureable thyroid-stimulating hormone (TSH) and free thyroxine (T 4 ). Upon questioning the patient reported classical thyrotoxic symptoms over the preceding weeks. Given the persistence of symptoms free tri-iodothyronine (T 3 ) was measured and found to be markedly elevated at 48.9 pmol/L (normal range: 3.1-6.8 pmol/L). No goitre or nodular disease was palpable in the neck. Historically there had never been any amiodarone usage. Radionucleotide thyroid uptake imaging ( 123 I) demonstrated significantly reduced tracer uptake in the thyroid. Upon further questioning the patient reported purchasing a weight loss product online from India which supposedly contained sibutramine. He provided one of the tablets and laboratory analysis confirmed the presence of T 3 in the tablet. Full symptomatic resolution and normalised thyroid function ensued upon discontinuation of the supplement. Free tri-iodothyronine (T 3 ) measurement may be useful in the presence of symptoms suggestive of thyrotoxicosis with discordant thyroid function tests.Thyroid uptake scanning can be a useful aid to differentiating exogenous hormone exposure from endogenous hyperthyroidism.Ingestion of thyroid hormone may be inadvertent in cases of exogenous thyrotoxicosis.Medicines and supplements sourced online for weight loss may contain thyroxine (T 4 ) or T 3 and should be considered as a cause of unexplained exogenous hyperthyroidism.

Hypothyroidism in coronary heart disease and its relation to selected risk factors

PubMed Central

Mayer, Otto; Šimon, Jaroslav; Filipovský, Jan; Plášková, Markéta; Pikner, Richard

2006-01-01

Introduction Hypothyroidism (HT) has been found a predictor of cardiovascular diseases. We aimed to ascertain the prevalence of HT in patients with manifest coronary heart disease (CHD), and to establish its association with conventional risk factors. Methods 410 patients, 6–24 months after hospitalization for acute coronary syndrome, and/or revascularization, were included into the cross-sectional study. Results The prevalence of thyroid dysfunction was found in males and females as follows: overt HT, ie, thyroid stimulating hormone (TSH) > 3.65 mIU/L and free thyroxine (fT4) < 9 pmol/L and/or L-thyroxine substitution, in 2.6% and 8.4%, respectively; subclinical HT (TSH >3.65, fT4 9–23 and no substitution) in 4.3% and 15.0%, respectively. Higher prevalence of HT was found in females with hypercholesterolemia, and in males and females with concomitant positive thyroid peroxydase antibodies. Hypothyroid subjects had higher total homocysteine in both genders and von Willebrand factor in males only. Hypothyroid females had higher total and LDL cholesterol, and were more often treated for diabetes. Conclusions HT was found highly prevalent in patient with clinical coronary heart disease, mainly in females, and was associated with several cardiovascular risk factors. PMID:17323605

Akt1 protects against germ cell apoptosis in the post natal mouse testis following lactational exposure to 6-N-propylthiouracil

EPA Science Inventory

Lactational exposure to 6-propyl-2-thio-uracil (PTU), a neonatal goitrogen, leads to increased testis size and sperm production in rodents. Aktl, a gene involved in cell survival and proliferation is also phosphorylated by thyroxine (T4). Therefore, we examined the requirement f...

Screening the ToxCast Phase 1, 2, and e1k Chemical Libraries for Inhibition of Deiodinase Type 1, 2 and 3 Enzyme Activity

EPA Science Inventory

Thyroid hormone (TH) homeostasis is dependent on multiple proteins for TH synthesis, transport, and peripheral metabolism and elimination. Deiodinase enzymes play an essential role in converting THs between active and inactive forms by converting the pro-hormone thyroxine (T4) to...

Screening the ToxCast Phase 1, 2, and e1k chemical libraries for inhibition of Deiodinase Types 1, 2 and 3 enzyme activity

EPA Science Inventory

Thyroid hormone (TH) homeostasis is dependent on multiple proteins for TH synthesis, transport, and peripheral metabolism and elimination. Deiodinase enzymes play an essential role in converting THs between active and inactive forms by deiodinating the pro-hormone thyroxine (T4) ...

Hippocampal Neurometabolite Changes in Hypothyroidism: An In Vivo (1) H Magnetic Resonance Spectroscopy Study Before and After Thyroxine Treatment.

PubMed

Singh, S; Rana, P; Kumar, P; Shankar, L R; Khushu, S

2016-09-01

The hippocampus is a thyroid hormone receptor-rich region of the brain. A change in thyroid hormone levels may be responsible for an alteration in hippocampal-associated function, such as learning, memory and attention. Neuroimaging studies have shown functional and structural changes in the hippocampus as a result of hypothyroidism. However, the underlying process responsible for this dysfunction remains unclear. Therefore, the present study aimed to investigate the metabolic changes in the brain of adult hypothyroid patients during pre- and post-thyroxine treatment using in vivo proton magnetic resonance spectroscopy ((1) H MRS). (1) H MRS was performed in both healthy control subjects (n = 15) and hypothyroid patients (n = 15) (before and after thyroxine treatment). The relative ratios of the neurometabolites were calculated using the linear combination model (LCModel). Our results revealed a significant decrease of glutamate (Glu) (P = 0.045) and myo-inositol (mI) (P = 0.002) levels in the hippocampus of hypothyroid patients compared to controls. No significant changes in metabolite ratios were observed in the hypothyroid patients after thyroxine treatment. The findings of the present study reveal decreased Glu/tCr and mI/tCr ratios in the hippocampus of hypothyroid patients and these metabolite alterations persisted even after the patients became clinically euthyroid subsequent to thyroxine treatment. © 2016 British Society for Neuroendocrinology.

Variable Suppression of Serum Thyroxine in Female Mice of Different Inbred Strains by Triiodothyronine Administered in Drinking Water

PubMed Central

Hamidi, Sepehr; Aliesky, Holly; Chen, Chun-Rong; Rapoport, Basil

2010-01-01

Background Recombinant-inbred mouse strains differ in their susceptibility to Graves'-like hyperthyroidism induced by immunization with adenovirus expressing the human thyrotropin (TSH) receptor. Because one genetic component contributing to this susceptibility is altered thyroid sensitivity to TSH receptor agonist stimulation, we wished to quantify thyroid responsiveness to TSH. For such studies, it is necessary to suppress endogenous TSH by administering L-3,5,3′-triiodothyronine (L-T3), with the subsequent decrease in serum thyroxine (T4) reflecting endogenous TSH suppression. Our two objectives were to assess in different inbred strains of mice (i) the extent of serum T4 suppression after L-T3 administration and (ii) the magnitude of serum T4 increase induced by TSH. Methods Mice were tail-bled to establish baseline-serum T4 before L-T3 administration. We initially employed a protocol of L-T3-supplemented drinking water for 7 days. In subsequent experiments, we injected L-T3 intraperitoneally (i.p.) daily for 3 days. Mice were then injected i.p. with bovine TSH (10 mU) and euthanized 5 hours later. Serum T4 was assayed before L-T3 administration, and before and after TSH injection. In some experiments, serum T3 and estradiol were measured in pooled sera. Results Oral L-T3 (3 or 5 μg/mL) suppressed serum T4 levels by 26%–64% in female BALB/c mice but >95% in males. T4 suppression in female B6 mice ranged from 0% to 90%. In C3H mice, L-T3 at 3 μg/mL was ineffective but 5 μg/mL achieved >80% serum T4 reduction. Unlike inbred mice, in outbred CF1 mice the same protocol was more effective: 83% in females and 100% suppression in males. The degree of T4 suppression was unrelated to baseline T4, T3, or estradiol, but was related to mouse weight and postmortem T3, with greater suppression in larger mice (outbred CF1 animals and inbred males). Among females with serum T4 suppression >80%, the increase in serum T4 after TSH injection was greater for BALB/c and C3H versus B6 mice. Moreover, the T4 increment was higher in female than in male BALB/c. Conclusions Our data provide important, practical information for future in vivo studies in inbred mice: we recommend that responses to TSH be performed in female animals injected with L-T3 i.p. to suppress baseline T4. PMID:20860425

Low free triiodothyronine levels predict symptomatic intracranial hemorrhage and worse short-term outcome of thrombolysis in patients with acute ischemia stroke.

PubMed

Qiu, Mingjing; Fang, Min; Liu, Xueyuan

2017-11-01

The aim of the study was to determine whether thyroid hormones level on admission in patients with ischemic stroke, treated with intravenous recombinant tissue type plasminogen activator (rtPA), was associated with symptomatic intracranial hemorrhage (sICH) and worse outcomes at 3 months.Patients with acute ischemic stroke (AIS) receiving intravenous rtPA thrombolytic treatment on our stroke unit between January 2015 and June 2016 were included in this study. Serum-free triiodothyronine (fT3), free thyroxine (fT4), total triiodothyronine (tT3), total thyroxine (tT4), and thyroid-stimulating hormone (TSH) were detected on admission. The endpoints were sICH, and poor functional outcomes at 3 and 6 months.In all, 159 patients (106 males; mean age 65.36 ± 10.02 years) were included. FT3 was independently associated with sICH (odds ratio [OR] 0.204, 95% confidence interval [CI] 0.065-0.642) and poor outcomes at 3 months (OR 0.396, 95% CI 0.180-1.764). The cut-off values of fT3 for sICH was 3.54 pg/mL (sensitivity 83%; specificity 83%; area under the curve 0.88). FT3 values ≤3.54 pg/mL increased risk for sICH by 3.16-fold (95% CI 0.75-1.0) compared with fT3 values >3.54 pg/mL.Low fT3 levels at admission were independently associated with sICH and worse outcomes at 3 months in AIS patients receiving rtPA thrombolytic therapy.

Low free triiodothyronine levels predict symptomatic intracranial hemorrhage and worse short-term outcome of thrombolysis in patients with acute ischemia stroke

PubMed Central

Qiu, Mingjing; Fang, Min; Liu, Xueyuan

2017-01-01

Abstract The aim of the study was to determine whether thyroid hormones level on admission in patients with ischemic stroke, treated with intravenous recombinant tissue type plasminogen activator (rtPA), was associated with symptomatic intracranial hemorrhage (sICH) and worse outcomes at 3 months. Patients with acute ischemic stroke (AIS) receiving intravenous rtPA thrombolytic treatment on our stroke unit between January 2015 and June 2016 were included in this study. Serum-free triiodothyronine (fT3), free thyroxine (fT4), total triiodothyronine (tT3), total thyroxine (tT4), and thyroid-stimulating hormone (TSH) were detected on admission. The endpoints were sICH, and poor functional outcomes at 3 and 6 months. In all, 159 patients (106 males; mean age 65.36 ± 10.02 years) were included. FT3 was independently associated with sICH (odds ratio [OR] 0.204, 95% confidence interval [CI] 0.065–0.642) and poor outcomes at 3 months (OR 0.396, 95% CI 0.180–1.764). The cut-off values of fT3 for sICH was 3.54 pg/mL (sensitivity 83%; specificity 83%; area under the curve 0.88). FT3 values ≤3.54 pg/mL increased risk for sICH by 3.16-fold (95% CI 0.75–1.0) compared with fT3 values >3.54 pg/mL. Low fT3 levels at admission were independently associated with sICH and worse outcomes at 3 months in AIS patients receiving rtPA thrombolytic therapy. PMID:29137061

Spatiotemporal patterns and relationships among the diet, biochemistry, and exposure to flame retardants in an apex avian predator, the peregrine falcon.

PubMed

Fernie, Kim J; Chabot, Dominique; Champoux, Louise; Brimble, Samantha; Alaee, Mehran; Marteinson, Sarah; Chen, Da; Palace, Vince; Bird, David M; Letcher, Robert J

2017-10-01

Flame retardants (FR) are industrial chemicals and some are proven environmental contaminants that accumulate in predatory birds. Few studies have examined the influence of diet on FR profiles in nestling raptors and the possible physiological implications of such FR exposure. The objectives of this research were (1) to determine spatial patterns of ≤ 48 polybrominated diphenyl ether (PBDE) congeners and ≤ 26 non-PBDE FRs, including organophosphate esters (OPEs), in nestling peregrine falcons (Falco peregrinus) across the Canadian Great Lakes-St. Lawrence River Basin (GL-SLR; 2010) and in the eastern Canadian Arctic (2007); (2) to identify temporal changes in FR concentrations from the mid-2000s to 2010 in GL-SLR peregrine nestlings; (3) to investigate the role of diet using stable isotopes on exposure patterns of quantifiable FRs; and (4) to assess possible associations between circulating FRs and total (T) thyroxine (TT 4 ) and triiodothyronine (TT 3 ), tocopherol, retinol and oxidative status (isoprostanes). The summed concentrations of the top 5 PBDEs (Σ 5 ) (BDE-47, -99, -100, -154, -153) were significantly higher in rural nestlings than urban nestlings in the GL-SLR, followed by the eastern Arctic nestlings. The PBDE congener profile of rural nestlings was dominated by BDE-99 (34‰), whereas BDE-209 (31‰) became dominant in the 2010 urban PBDE profile marking a shift since the mid-2000s. Low (ppb) concentrations of 25 novel non-PBDE FRs (e.g., 1,2-bis-(2,4,6-tribromophenoxy)ethane (BTBPE), decabromodiphenylethane (DBDPE)) were measured in the nestlings in at least one region, with the first report in peregrines of 15 novel non-PBDE FRs (e.g., 2-ethyl-1-hyxyl 2,3,4,5-tetrabromobenzoate (EHTBB), pentabromo allyl ether (PBPAE), tetrabromoethylcyclohexane (α-, β-DBE-DBCH)) as well as of tris (2-butoxyethyl) phosphate (TBOEP) (0-7.5ng/g ww) > tris(2-chloroisopropyl) phosphate (TCIPP) (0.1-5.5ng/g ww) > tris(2-chloroethyl) phosphate (TCEP) (0.02-2.0ng/g ww) > tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) (0-1.0ng/g ww). Within the GL-SLR, the urban nestlings' diet had significantly more terrestrial sources (greater δ 13 C values) than the broader, more aquatic-based diet of rural peregrines. Dietary source (δ 13 C) was significantly associated with concentrations of Σ 5 PBDE, BDE-209, EHTBB, and 2,2-4,4',5,5'-hexabromobiphenyl (BB-153), with trophic level (δ 15 N) also positively associated with BDE-209 levels. Compared to urban nestlings, the rural nestlings had significantly lower circulating concentrations of thyroxine (TT 4 ), triiodothyronine (TT 3 ), a greater proportion of TT 3 relative to TT 4 (TT 3 :TT 4 ), tocopherol and oxidative status (isoprostanes), but higher retinol levels; the most recalcitrant PBDE congener, BDE-153, in combination with low concentrations of some novel FRs, particularly octabromotrimethylphenyllindane (OBIND), may influence circulating thyroid hormones, especially TT 4 , and retinol levels of peregrine falcon nestlings. These associations of FR-endocrine-biochemical measures suggest possible exposure-related changes in these birds and further study is warranted. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Determination of autoantibodies to thyroglobulin, thyroxine and triiodothyronine in canine serum.

PubMed

Patzl, M; Möstl, E

2003-03-01

Enzyme immunoassays (EIAs) for the determination of autoanti-bodies (AA) to thyroid antigens in canine serum were developed. Streptavidin (SA) was immobilized as capture molecule on microtitreplates (MTP). Thyroglobulin (Tg) purified from canine thyroids and the thyroid hormones thyroxine and triiodothyronine (T3 and T4) were conjugated to biotin labelling reagents and attached to the MTP over the SA-biotin bridge. Bound AA were detected with anti-dog-immunoglobulin G (IgG) labelled with horseradish peroxidase. Serum samples from dogs which were allotted to four groups were analysed: A (n = 31), biochemical evidence of hypothyroidism; B (n = 76), clinical signs of hypothyroidism; C (n = 47), euthyroid with non-thyroidal disease; D (n = 186), clinically healthy. The validity of the assays was tested with two different methods. After thiophilic absorption chromatography of positive sera, a positive reaction in the EIA was only detected in those fractions which coeluted with the canine IgG standard. Furthermore, the positive reaction was blocked by the addition of the corresponding antigen. In 55% of the hypothyroid dogs AA to Tg and/or T3 and T4, respectively, were found (up to a titre of 1 : 1600). In group B 34% of the dogs were diagnosed positive, but the titre was lower (up to 1 : 400). In the groups C and D the number of dogs with AA and their titre was significantly lower. Two different methods for distinguishing positive and negative test results were compared in order to increase the specificity of the tests without decreasing the sensitivity. The EIAs are precise and based on high agreement with previous reported assays able to discriminate dogs with thyroiditis from healthy ones. These assays represent a good alternative to the isotope assays generally used for the analysis of AA to T4 and T3.

Transient hypothyroidism in the newborn: to treat or not to treat

PubMed Central

Kanike, Neelakanta; Davis, Ajuah

2017-01-01

Transient congenital hypothyroidism (CH) refers to a temporary deficiency of thyroid hormone identified after birth, with low thyroxine (T4) and elevated thyrotropin (TSH), which later recovers to improved thyroxine production, typically in first few months of infancy. Approximately 17% to 40% of children diagnosed with CH by newborn screening (NBS) programs were later determined to have transient hypothyroidism. Causes of transient CH are prematurity, iodine deficiency, maternal thyrotropin receptor blocking antibodies, maternal intake of anti-thyroid drugs, maternal or neonatal iodine exposure, loss of function mutations and hepatic hemangiomas. The classic clinical symptoms and signs of CH are usually absent immediately after birth in vast majority of infants due to temporary protection from maternal thyroxine. NBS has been largely successful in preventing intellectual disability by early detection of CH by performing thyroid function tests in infants with abnormal screening results. In this review we present the evidence for decision making regarding treatment vs. withholding treatment in infants with transient CH and present a rational approach to identifying transient CH based on American Academy of Pediatrics (AAP) recommendation. PMID:29184815

Induction of a hypothyroid state during juvenile development delays pubertal reactivation of the neuroendocrine system governing luteinising hormone secretion in the male rhesus monkey (Macaca mulatta).

PubMed

Mann, D R; Bhat, G K; Stah, C D; Pohl, C R; Plant, T M

2006-09-01

The present study aimed to determine the influence of thyroid status on the timing of the pubertal resurgence in gonadotrophin-releasing hormone pulse generator activity [tracked by circulating luteinising hormone (LH) levels] in male rhesus monkeys. Six juvenile monkeys were orchidectomised and then treated with the antithyroid drug, methimazole, from 15-19 months until 36 months of age, at which time thyroxine (T(4)) replacement was initiated. Four additional agonadal monkeys served as controls. Blood samples were drawn weekly for hormonal assessments. Body weight, crown-rump length and bone age were monitored at regular intervals. By 8 weeks of methimazole treatment, plasma T(4) had fallen sharply, and the decline was associated with a plasma thyroid-stimulating hormone increase. In controls, plasma LH levels remained undetectable until the pubertal rise occurred at 29.3 +/- 0.2 months of age. This developmental event occurred in only half of the methimazole-treated animals before 36 months of age when T(4) replacement was initiated. The hypothyroid state was associated with a profound arrest of growth and bone maturation, but increased body mass indices and plasma leptin levels. T(4) replacement in methimazole-treated monkeys was associated with the pubertal rise in LH in the remaining three animals and accelerated somatic development in all six animals. Although pubertal resurgence in LH secretion occurred at a later chronological age in methimazole-treated animals compared to controls, bone age, crown-rump length and body weight at that time did not differ between groups. There were no long-term differences in plasma prolactin between groups. We conclude that juvenile hypothyroidism in male primates causes a marked delay in the pubertal resurgence of LH secretion, probably occasioned at the hypothalamic level. Whether this effect is meditated by an action of thyroid hormone directly on the hypothalamus or indirectly as a result of the concomitant deficit in somatic development remains to be determined.

Median-lower normal levels of serum thyroxine are associated with low triiodothyronine levels and body temperature in patients with central hypothyroidism.

PubMed

Hirata, Yu; Fukuoka, Hidenori; Iguchi, Genzo; Iwahashi, Yasuyuki; Fujita, Yasunori; Hari, Yusuke; Iga, Makiko; Nakajima, Shinsuke; Nishimoto, Yuki; Mukai, Miki; Hirota, Yushi; Sakaguchi, Kazuhiko; Ogawa, Wataru; Takahashi, Yutaka

2015-08-01

Although it has been recommended that serum free thyroxine (FT4) levels should be targeted to middle-upper normal levels during levothyroxine (l-T4) replacement therapy in patients with central hypothyroidism (CeH), the rationale has not been clarified. A retrospective single-center study enrolled 116 patients with hypothyroidism (CeH, n=32; total thyroidectomy (Tx), n=22; primary hypothyroidism (PH), n=33; and control benign thyroid nodule (C), n=29). The patients had received L-T4 therapy at the Kobe University Hospital between 2003 and 2013. They were stratified according to serum FT4 level (≥ 1.10 or <1.10 ng/dl), and body temperature (BT), serum free triiodothyronine (FT3) levels, FT3/FT4 ratio, and lipid profiles were compared. The effect of GH replacement therapy on thyroid function was also analyzed. FT3 levels and FT3/FT4 ratios were significantly lower in patients with CeH than in patients with PH (P<0.05) or C (P<0.05). In patients with FT4 <1.10 ng/dl, BT was significantly lower in patients with CeH (P=0.002) and Tx (P=0.005) than in patients with PH, whereas no differences were found in patients with FT4 ≥ 1.10 ng/dl. In patients with CeH, FT3 levels were higher in those with GH replacement therapy (P=0.018). In CeH, patients with median-lower normal levels of serum FT4 exhibited lower serum FT3 levels and lower BT. These results support the target levels of serum FT4 as middle-upper normal levels during l-T4 replacement therapy in patients with CeH. © 2015 European Society of Endocrinology.

Amelioration of L-thyroxine-induced hyperthyroidism by coumarin (1,2-benzopyrone) in female rats.

PubMed

Panda, Sunanda; Kar, Anand

2007-11-01

1. The efficacy of coumarin (1,2-benzopyrone) was examined for the regulation of hyperthyroidism in female rats. 2. Coumarin was administered (10 mg/kg per day for 15 days) to l-thyroxine (L-T(4))-induced hyperthyroid as well as to euthyroid rats and changes in serum concentrations of thyroid hormones and in associated parameters, such as serum cholesterol, activity of hepatic 5'-monodeiodinase (5'DI) and glucose-6-phosphatase (G-6-Pase), glycogen content, bodyweight and daily food consumption, were analysed. Simultaneously, changes in hepatic lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were also investigated. 3. Although L-T(4) administration increased serum levels of thyroid hormones, the activity of hepatic 5'DI, G-6-Pase and LPO and daily food consumption, it decreased the level of serum cholesterol, hepatic glycogen content and the activities of anti-oxidant enzymes, such as SOD, CAT and GSH. 4. However, simultaneous administration of coumarin for 15 days to a group of hyperthyroid animals reversed most of the aforementioned changes, indicating its potential to ameliorate hyperthyroidism. Moreover, the drug did not increase, but rather decreased, hepatic LPO, suggesting its safe nature. 5. The present findings reveal a positive role for coumarin in the regulation of hyperthyroidism without any hepatotoxicity. It also appears that the test compound inhibits thyroid function at both a glandular level and at the level of peripheral conversion of T(4) to tri-iodothyronine.

Treatment of subclinical hypothyroidism in pregnancy using fixed thyroxine daily doses of 75 μg.

PubMed

Penin, Manuel; Trigo, Cristina; López, Yolanda; Barragáns, María

2014-01-01

Treatment of hypothyroid pregnant women is usually calculated based on weight (1 μg/kg/day) and TSH levels. This study assessed the usefulness of treating these women with a fixed dose of 75 μg/day. All women with pregnancy diagnosed from January to August 2012 in the Vigo Health Area (Spain) without previous diagnosis of thyroid disease or thyroxine treatment and with TSH levels over 4,5 mUI/ml were enrolled by consecutive sampling. All 116 women in the sample were treated with a fixed daily dose of thyroxine 75 μg-thyroxine levels were measured at two, four, and six months, and thyroxine dose was modified if TSH level was lower than 0.3 or higher than 4.5 mUI/ml. A woman had a TSH level less than 0.3 mUI/ml in a test; reduction of thyroxine dose to 50 μg/day allowed for maintaining TSH level within the desired range until delivery. Six women had TSH levels over 4.5 mUI/ml in one test; in all of them, increase in thyroxine dose to 100 μg/day allowed for maintaining the level within the desired range until delivery. Fixed daily doses of thyroxine 75 μg allowed for achieving goal TSH levels in most of our pregnant women with subclinical hypothyroidism, irrespective of their weight and baseline TSH level. Copyright © 2013 SEEN. Published by Elsevier Espana. 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.

[Combined l-thyroxine and l-triiodothyronine replacement therapy in congenital hypothyroidism].

PubMed

Péter, Ferenc; Muzsnai, Agota

2013-05-12

L-thyroxine replacement therapy is the treatment of choice for hypothyroidism. Recently, several studies suggested to complete it with l-triiodothyronine in acquired hypothyroidism. To study the role of combined l-thyroxine and l-triiodothyronine therapy in special cases with congenital hypothyroidism. Data of 16 patients (age: 11.9 ± 6.3 years; mean ± SD) are presented who had high serum free thyroxine values or even above the upper limit of reference range (21.16 ± 2.5 pmol/l) together with nonsuppressed TSH levels (15.7 ± 5.7 mIU/l), and therefore received l-triiodothyronine in completion (0.18 ± 0.09 μg/kg) once a day. The combined replacement therapy resulted in a rapid improvement of the hormone parameters (TSH: 4.2 ± 3.15 mIU/l; free thyroxine: 16.55 ± 2.4 and free triiodothyronine: 7.4 ± 1.8 pmol/l). The efficiency of this combined therapy proved to be more evident (TSH: 4.33 ± 3.2 mIU/l; free thyroxine: 16.85 ± 3.1 and free triiodothyronine: 6.4 ± 0.85 pmol/l) in 10 patients treated for a longer period of time (duration of treatment: 2.9 ± 2.0 years). The dose of thyroxine substitution decreased from 2.6 ± 0.9 to 2.18 ± 0.6 μg/kg/day), the ratio of these hormones was between 5:1 and 19:1 and the quotient of free fractions was normalized (3.8 ± 0.4→2.6 ± 0.3) during the replacement therapy. According to the observation of the authors a serious disturbance of feed-back mechanism may develop in some (>5%) children with congenital hypothyroidism (increased TSH release despite elevated free thyroxine level) after normal function of the feed-back system for years. Hormone parameters of these patients improve, then become normal on combined therapy supporting the rationale for this treatment method.

Dietary calcium induced cytological and biochemical changes in thyroid.

PubMed

Chandra, Amar K; Goswami, Haimanti; Sengupta, Pallav

2012-09-01

Certain epidemiological studies revealed correlation between hard water consumption (with high calcium) and thyroid size of the population, though the possible alterations in thyroid physiology upon calcium exposure are still inconclusive. Adult male Wistar strain rats were subjected to calcium treatment at the doses of 0.5g%, 1.0g% and 1.5g% calcium chloride (CaCl(2)) for 60 days. The parameters studied were - thyroid gland weight, histopathology, histomorphometry; thyroid peroxidase (TPO), 5'-deiodinase I (DI), sodium-potassium adenosine triphosphatase (Na(+)-K(+)-ATPase) activities; serum total and free thyroxine (tT4, fT4), total and free triiodothyronine (tT3, fT3), thyroid stimulating hormone (TSH) levels. Enlargement of thyroid with hypertrophic and hyperplastic changes, retarded TPO and 5'-DI but enhanced Na(+)-K(+)-ATPase activities, augmented serum total and free T4 and TSH but decreased total and free T3 levels and low T3/T4 ratio (T3:T4) were observed in the treated groups. All these findings indicate development of goitrogenesis upon exposure to excessive dietary calcium. Copyright © 2012 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2015-01-01

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

Thyroid 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.

Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2012-08-01

as they relate to functional outcome. At 6 months post injury, patients will be screened for anterior pituitary function 121 subjects have been...are indicative of anterior pituitary function, including somatomedin (IGF-1), thyroid stimulating hormone (TSH), thyroxine (Free T4), prolactin, and...incidence of single and multiple pituitary hormone deficiencies. The clinical characteristics, MRI imaging results, EEG and MEG results of the

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

PubMed

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

2017-05-01

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

Specific labeling of the thyroxine binding site in thyroxine-binding globulin: determination of the amino acid composition of a labeled peptide fragment isolated from a proteolytic digest of the derivatized protein.

PubMed

Tabachnick, M; Perret, V

1987-08-01

[125I] Thyroxine has been covalently bound to the thyroxine binding site in thyroxine-binding globulin by reaction with the bifunctional reagent, 1,5-difluoro-2,4-dinitrobenzene. An average of 0.47 mol of [125I] thyroxine was incorporated per mol protein; nonspecific binding amounted to 8%. A labeled peptide fragment was isolated from a proteolytic digest of the derivatized protein by HPLC and its amino acid composition was determined. Comparison with the amino acid sequence of thyroxine-binding globulin indicated partial correspondence of the labeled peptide with two possible regions in the protein. These regions also coincide with part of the barrel structure present in the closely homologous protein, alpha 1-antitrypsin.

Effect of Thyroxin Treatment on Carotid Intima-Media Thickness (CIMT) Reduction in Patients with Subclinical Hypothyroidism (SCH): a Meta-Analysis of Clinical Trials.

PubMed

Aziz, Muhammad; Kandimalla, Yugandhar; Machavarapu, Archana; Saxena, Anshul; Das, Sankalp; Younus, Adnan; Nguyen, Michelle; Malik, Rehan; Anugula, Dixitha; Latif, Muhammad A; Humayun, Choudhry; Khan, Idrees M; Adus, Ali; Rasool, Aisha; Veledar, Emir; Nasir, Khurram

2017-07-01

Research shows that subclinical hypothyroidism (SCH) is related to an increased carotid intima-media thickness (CIMT), a surrogate marker of subclinical cardiovascular disease (CVD). It is controversial whether or not SCH should be treated to reduce CVD morbidity and mortality. This meta-analysis aimed to determine whether SCH is associated with an increase in CIMT as compared to Euthyroidism (EU) and whether thyroxin (T4) treatment in SCH can reverse the change in CIMT. Two independent reviewers conducted an extensive database research up to December 2016. A total of 12 clinical trials discussed the effect of Thyroxin on CIMT values at pre- and post-treatment in subjects with SCH. CIMT was significantly higher among SCH (n=280) as compared to EU controls (n=263) at baseline; the pooled weighted mean difference (WMD) of CIMT was 0.44 mm [95% confidence interval (CI) 0.14, 0.74], p=0.004; I 2 =65%. After treatment with thyroxin in subjects with SCH (n=314), there was a statistically significant decrease in CIMT from pre- to post-treatment; the pooled WMD of CIMT decrease was [WMD －0.32; 95% CI (－0.47, －0.16), p=＜0.0001; I 2 =2%], and it was no longer different from EU controls [WMD 0.13 mm; 95% CI (－0.04, 0.30); p=0.14; I 2 =27%]. The total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) were higher in SCH as compared to EU controls and decreased significantly after treatment with thyroxin. This meta-analysis shows that thyroxin therapy in subjects with SCH significantly decreases CIMT and improves lipid profile, modifiable CVD risk factors. Thyroid hormone replacement in subjects with SCH may play a role in slowing down or preventing the progression of atherosclerosis.

Effect of Thyroxin Treatment on Carotid Intima–Media Thickness (CIMT) Reduction in Patients with Subclinical Hypothyroidism (SCH): a Meta-Analysis of Clinical Trials

PubMed Central

Aziz, Muhammad; Kandimalla, Yugandhar; Machavarapu, Archana; Saxena, Anshul; Das, Sankalp; Younus, Adnan; Nguyen, Michelle; Malik, Rehan; Anugula, Dixitha; Latif, Muhammad A.; Humayun, Choudhry; Khan, Idrees M.; Adus, Ali; Rasool, Aisha; Veledar, Emir

2017-01-01

Aim: Research shows that subclinical hypothyroidism (SCH) is related to an increased carotid intima –media thickness (CIMT), a surrogate marker of subclinical cardiovascular disease (CVD). It is controversial whether or not SCH should be treated to reduce CVD morbidity and mortality. This meta-analysis aimed to determine whether SCH is associated with an increase in CIMT as compared to Euthyroidism (EU) and whether thyroxin (T4) treatment in SCH can reverse the change in CIMT. Methods: Two independent reviewers conducted an extensive database research up to December 2016. A total of 12 clinical trials discussed the effect of Thyroxin on CIMT values at pre- and post-treatment in subjects with SCH. Results: CIMT was significantly higher among SCH (n = 280) as compared to EU controls (n = 263) at baseline; the pooled weighted mean difference (WMD) of CIMT was 0.44 mm [95% confidence interval (CI) 0.14, 0.74], p = 0.004; I2 = 65%. After treatment with thyroxin in subjects with SCH (n = 314), there was a statistically significant decrease in CIMT from pre- to post-treatment; the pooled WMD of CIMT decrease was [WMD −0.32; 95% CI (−0.47, −0.16), p = < 0.0001; I2 = 2%], and it was no longer different from EU controls [WMD 0.13 mm; 95% CI (−0.04, 0.30); p = 0.14; I2 = 27%]. The total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) were higher in SCH as compared to EU controls and decreased significantly after treatment with thyroxin. Conclusion: This meta-analysis shows that thyroxin therapy in subjects with SCH significantly decreases CIMT and improves lipid profile, modifiable CVD risk factors. Thyroid hormone replacement in subjects with SCH may play a role in slowing down or preventing the progression of atherosclerosis. PMID:28566564

Down's syndrome and thyroid disorder.

PubMed

Dinani, S; Carpenter, S

1990-04-01

The thyroid status of 106 adults with Down's syndrome was assessed. Six were previously diagnosed as hypothyroid and were already receiving thyroxine. A further 37 patients showed abnormal thyroid function. Biochemical evidence of hypothyroidism (T4 less than 50 nmol/l and T.S.H. greater than 4 mu/less than) was found in one person. Six patients were found to have an unequivocally elevated T.S.H. but normal T4 (T4 greater than 50 nmol/l and T.S.H. greater than 20 mu/l) and 29 were found to have a modest elevation of T.S.H. but normal T4 concentration (T4 greater than 50 nmol/l and T.S.H. between 4 and 20 mu/l). There was one patient with mild thyrotoxicosis (T4 = 180 nmol/l and T.S.H. less than 0.1 mu/l). Clinical findings were of little use in making a diagnosis of hypothyroidism in this group of patients. A raised level of thyroid microsomal auto-antibodies was found in about a third of the patients, this occurred more commonly in females and slightly more often in those with a raised thyroid stimulating hormone. The importance of this is discussed. Recommendations for regular biochemical screening are made.

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

PubMed Central

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

2010-01-01

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

Pediatric Reference Intervals for Free Thyroxine and Free Triiodothyronine by Equilibrium Dialysis-Liquid Chromatography-Tandem Mass Spectrometry.

PubMed

La'ulu, Sonia L; Rasmussen, Kyle J; Straseski, Joely A

2016-03-05

Thyroid hormone concentrations fluctuate during growth and development. To accurately diagnose thyroid disease in pediatric patients, reference intervals (RIs) should be established with appropriate age groups from an adequate number of healthy subjects using the most exact methods possible. Obtaining statistically useful numbers of healthy patients is particularly challenging for pediatric populations. The objective of this study was to determine non-parametric RIs for free thyroxine (fT4) and free triiodothyronine (fT3) using equilibrium dialysis-high performance liquid chromatography-tandem mass spectrometry with over 2200 healthy children 6 months-17 years of age. Subjects were negative for both thyroglobulin and thyroid peroxidase autoantibodies and had normal thyrotropin concentrations. The study included 2213 children (1129 boys and 1084 girls), with at least 120 subjects (average of 125) from each year of life, except for the 6 month to 1 year age group (n=96). Non-parametric RIs (95th percentile) for fT4 were: 18.0-34.7 pmol/L (boys and girls, 6 months-6 years) and 14.2-25.7 pmol/L (boys and girls, 7-17 years). RIs for fT3 were: 5.8-13.1 pmol/L (girls, 6 months-6 years); 5.7-11.8 pmol/L (boys, 6 months-6 years); 5.7-10.0 pmol/L (boys and girls, 7-12 years); 4.5-8.6 pmol/L (girls, 13-17 years); and 5.2-9.4 pmol/L (boys, 13-17 years). Numerous significant differences were observed between pediatric age groups and previously established adult ranges. This emphasizes the need for well-characterized RIs for thyroid hormones in the pediatric population.

Pediatric Reference Intervals for Free Thyroxine and Free Triiodothyronine by Equilibrium Dialysis-Liquid Chromatography-Tandem Mass Spectrometry

PubMed Central

La’ulu, Sonia L.; Rasmussen, Kyle J.; Straseski, Joely A.

2016-01-01

Objective: Thyroid hormone concentrations fluctuate during growth and development. To accurately diagnose thyroid disease in pediatric patients, reference intervals (RIs) should be established with appropriate age groups from an adequate number of healthy subjects using the most exact methods possible. Obtaining statistically useful numbers of healthy patients is particularly challenging for pediatric populations. The objective of this study was to determine non-parametric RIs for free thyroxine (fT4) and free triiodothyronine (fT3) using equilibrium dialysis-high performance liquid chromatography-tandem mass spectrometry with over 2200 healthy children 6 months-17 years of age. Methods: Subjects were negative for both thyroglobulin and thyroid peroxidase autoantibodies and had normal thyrotropin concentrations. The study included 2213 children (1129 boys and 1084 girls), with at least 120 subjects (average of 125) from each year of life, except for the 6 month to 1 year age group (n=96). Results: Non-parametric RIs (95th percentile) for fT4 were: 18.0-34.7 pmol/L (boys and girls, 6 months-6 years) and 14.2-25.7 pmol/L (boys and girls, 7-17 years). RIs for fT3 were: 5.8-13.1 pmol/L (girls, 6 months-6 years); 5.7-11.8 pmol/L (boys, 6 months-6 years); 5.7-10.0 pmol/L (boys and girls, 7-12 years); 4.5-8.6 pmol/L (girls, 13-17 years); and 5.2-9.4 pmol/L (boys, 13-17 years). Conclusion: Numerous significant differences were observed between pediatric age groups and previously established adult ranges. This emphasizes the need for well-characterized RIs for thyroid hormones in the pediatric population. PMID:26758817

Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison's disease with primary hypothyroidism

PubMed Central

Sahoo, Jaya Prakash; Selviambigapathy, Jayakumar; Kamalanathan, Sadishkumar; Nagarajan, K.; Vivekanandan, Muthupillai

2016-01-01

Background: Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT) in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with primary hypothyroidism. Materials and Methods: This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (<83 nmol/L) with high plasma adrenocorticotropic hormone (>22 pmol/L) and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical) was defined as high thyroid stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Results: Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. Conclusions: The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations. PMID:27042409

Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison's disease with primary hypothyroidism.

PubMed

Sahoo, Jaya Prakash; Selviambigapathy, Jayakumar; Kamalanathan, Sadishkumar; Nagarajan, K; Vivekanandan, Muthupillai

2016-01-01

Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT) in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with primary hypothyroidism. This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (<83 nmol/L) with high plasma adrenocorticotropic hormone (>22 pmol/L) and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical) was defined as high thyroid stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations.

Circulating rotavirus-specific T cells have a poor functional profile

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

Parra, Miguel; Herrera, Daniel; Jácome, María Fernanda

Frequencies of circulating T cells producing IFN-γ, TNF-α, and IL-2, and percentages of T cells proliferating after stimulation with rotavirus (RV), tetanus toxoid, and influenza were evaluated in PBMC derived from healthy adults and children. In addition, the potential anergic state of RV-specific T cells was analyzed by stimulation of PBMC with RV antigen in the presence of three anergy inhibitors (rIL-2, rIL-12, or DGKα-i). The quality and magnitude of RV-T cell responses were significantly lower than those of tetanus toxoid and influenza antigens. RV-CD4 T cell response was enriched in monofunctional IFN-γ{sup +} cells, while influenza-CD4 and tetanus toxoid-CD4more » T cell responses were enriched in multifunctional T cells. Moreover, rIL-2 – unlike rIL-12 or DGKα-i – increased the frequencies of RV-CD4 TNF-α{sup +}, CD4 IFN-γ{sup +}, and CD8 IFN-γ{sup +} cells. Thus, circulating RV-T cells seem to have a relatively poor functional profile that may be partially reversed in vitro by the addition of rIL-2. - Highlights: • The quality and magnitude of circulating RV-T cell responses are relatively poor. • Circulating RV-CD4 T cells are enriched in monofunctional IFN-γ+ cells. • Treatment with rIL-2 increased the frequencies of cytokine secreting RV-T cells.« less

Etiological evaluation of primary congenital hypothyroidism cases

PubMed Central

Bezen, Diğdem; Dilek, Emine; Torun, Neşe; Tütüncüler, Filiz

2017-01-01

Aim Primary congenital hypothyroidism is frequently seen endocrine disorder and one of the preventable cause of mental retardation. Aim of study was to evaluate the frequency of permanent/transient hypothyrodism, and to detect underlying reason to identfy any marker which carries potential to discriminate permanent/transient form. Material and Methods Forty eight cases older than 3 years of age, diagnosed as primary congenital hypothyroidism and started thyroxin therapy in newborn-period, and followed up between January 2007–June 2013 were included in the study. Thyroid hormon levels were evaluated and thyroid ultrasonography was performed in cases who are at the end of their 3 years of age, after 6 weeks of thyroxine free period. Thyroid sintigraphy was performed if serum thyroid-stimulating hormone was high (≥ 5 mIU/mL) and perchlorate discharge test was performed if uptake was normal or increased on sintigraphy. Cases with thyroid-stimulating hormone levels ≥ 5 mIU/mL were defined as permanent primary congenital hypothyroidism group and as transient primary congenital hypothyroidism group with normal thyroid hormones during 6 months. Results The mean age was 3.8±0.7 years. Mean diagnosis age was 16.6±6.5 days and 14 cases (29.2%) were diagnosed by screening program of Ministry of Health. There were 23 cases (14F, 9M) in permanent primary congenital hypothyroidism group and 12 (52.2%) of them were dysgenesis (8 hypoplasia, 4 ectopia), and 11 (47.8%) dyshormonogenesis. In transient primary congenital hypothyroidism group, there were 25 cases (17M, 8F). The mean thyroid-stimulating hormone levels at diagnosis were similar in two groups. The mean thyroxin dose in permanent primary congenital hypothyroidism group was significantly higher than transient group at the time of thyroxin cessation (2.1±0.7, 1.5±0.5 mg/kg/d, respectively, p=0.004). Thyroxin dose ≥1.6 mcg/kg/d was 72% sensitive and 69.6% specific for predicting permenant primary congenital hypothyroidism. Conclusions Transient primary congenital hypothyroidism is more frequent than expected and found often in males in the primary congenital hypothyroidism cases, started thyroxin therapy in neonatal period. While fT4, thyroid-stimulating hormone, Tg levels at diagnosis do not predict transient/permenant primary congenital hypothyroidism, thyroxin dose before the therapy cessation at the age of 3 may make the distinction between transient/permenant primary congenital hypothyroidism. PMID:28747839

Effects of thyroid state on respiration of perfused rat and guinea pig hearts

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

Read, L.C.; Wallace, P.G.; Berry, M.N.

1987-09-01

The effects of thyroid state on the respiration of the isolated heart were investigated using retrograde perfused rat and guinea pig hearts. In both species, hypothyroidism caused a marked depression in circulating thyroid hormone concentrations and in the respiration of the isolated, retrograde perfused heart. Hypothyroidism was caused by injecting animals with Na{sup 131}I. The effects on myocardial respiration could be attributed to changes in the contraction frequency and in the oxygen consumption per beat, with little contribution from basal respiration. Treatment of animals with thyroxine elevated plasma thyroid hormones to a similar extent in rats and guinea pigs. Inmore » the latter, thyroxine treatment was associated with substantial increases in the contraction frequency and the oxygen consumption per beat of the isolated heart. In contrast, only small changes were apparent in the retrograde perfused rat heart, observations that were confirmed in rat hearts perfused at near physiological work loads. It was concluded that rat hearts isolated from normal animals function at near maximal thyroid state, in contrast to the guinea pig heart, which requires higher circulating concentrations of thyroid hormones to attain maximal responses.« less

Acute phase response and plasma carotenoid concentrations in older women: findings from the nun study.

PubMed

Boosalis, M G; Snowdon, D A; Tully, C L; Gross, M D

1996-01-01

This cross-sectional study investigated whether the acute phase response was associated with suppressed circulating levels of antioxidants in a population of 85 Catholic sisters (nuns) ages 77-99 y. Fasting blood was drawn to determine the presence of an acute phase response, as defined by an elevation in the serum concentration of C-reactive protein. Serum concentrations of albumin, thyroxine-binding prealbumin, zinc, copper, and fibrinogen were determined as were plasma concentrations of carotenoids and alpha tocopherol. Results showed that the presence of an acute phase response was associated with (1) an expected significant decrease in the serum concentrations of albumin (p < 0.001) and thyroxine-binding prealbumin (p < 0.001); (2) an expected significant increase in copper (p < 0.001) and fibrinogen (p = 0.003); and (3) a significant decrease in the plasma concentrations of lycopene (p = 0.03), alpha carotene (p = 0.02), beta carotene (p = 0.02), and total carotenoids (p = 0.01). The acute phase response was associated with decreased plasma levels of the antioxidants lycopene, alpha carotene, and beta carotene. This decrease in circulating antioxidants may further compromise antioxidant status and increase oxidative stress and damage in elders.

Alteration of Hemostatic Parameters in Patients with Different Levels of Subclinical Hypothyroidism and the Effect of L-thyroxine Treatment.

PubMed

Gao, Fang; Wang, Guangya; Xu, Jinxiu

2017-01-01

Subclinical hypothyroidism (SH) is associated with hypercoagulability and hypofibrinolysis. The objective of this study was to assess the effect of L-thyroxine (L-T4) treatment and to evaluate changes in the hemostatic abnormalities of patients with varying severities of SH. We measured tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer (DDI), fibrinogen (FIB), platelet counts (PLT), mean platelet volume (MPV), platelet distribution width (PDW), activated partial thromboplastin time (APTT), and prothrombin time (PT) in 149 female subjects. The prospective study included 54 patients in the control group, 53 patients with 4.2 μIU/mL

Differentiating Graves' disease from subacute thyroiditis using ratio of serum free triiodothyronine to free thyroxine.

PubMed

Sriphrapradang, Chutintorn; Bhasipol, Adikan

2016-09-01

The measurement of free thyroid hormone, instead of the total form, is more commonly used in current practice. We aimed to evaluate the usefulness of the ratio of serum free triiodothyronine (FT3, pg/mL) to free thyroxine (FT4, ng/dL) for differentiating Graves' disease from subacute thyroiditis. Medical records of thyrotoxic patients aged >15 years who had measurement of FT3, FT4 and thyrotropin on the first diagnosis of thyrotoxicosis before initiating treatment were retrospectively reviewed. Data were collected from all clinics, and were not limited to the endocrine clinic. Pregnant women were excluded. A total of 548 patients (468 with Graves' disease, 40 with subacute thyroiditis and 40 with toxic adenoma/multinodular goiter) were recruited. Mean age was 43.9 ± 15.4 years. Most were female 434 (79.2%), and goiter was present in 55.3%. Prevalence of T3-toxicosis and T4-toxicosis were 5.6% and 6.6%, respectively. Mean FT3/FT4 ratios were 4.62 ± 2 (10(-2) pg/ng) in patients with Graves' disease and 2.73 ± 0.5 in subacute thyroiditis. The area under the ROC curve of the FT3/FT4 ratio for diagnosis of Graves' disease was 0.83 (95%CI, 0.76-0.91). Cutoff level of this ratio >4.4 offered sensitivity of 47.2% and specificity of 92.8%. FT3/FT4 ratio of >4.4 (10(-2) pg/ng) may help in differentiating the cause of thyrotoxicosis.

Diagnosis of hyperthyroidism in cats with mild chronic kidney disease.

PubMed

Wakeling, J; Moore, K; Elliott, J; Syme, H

2008-06-01

In cats with concurrent hyperthyroidism and non-thyroidal illnesses such as chronic kidney disease, total thyroxine concentrations are often within the laboratory reference range (19 to 55 nmol/l). The objective of the study was to determine total thyroxine, free thyroxine and/or thyroid-stimulating hormone concentrations in cats with mild chronic kidney disease. Total thyroxine, free thyroxine and thyroid-stimulating hormone were measured in three groups. The hyperthyroidism-chronic kidney disease group (n=16) had chronic kidney disease and clinical signs compatible with hyperthyroidism but a plasma total thyroxine concentration within the reference range. These cats were subsequently confirmed to be hyperthyroid at a later date. The chronic kidney disease-only group (n=20) had chronic kidney disease but no signs of hyperthyroidism. The normal group (n=20) comprised clinically healthy senior (>8 years) cats. In 4 of 20 euthyroid chronic kidney disease cats, free thyroxine concentrations were borderline or high (> or =40 pmol/l). In the hyperthyroidism-chronic kidney disease group, free thyroxine was high in 15 of 16 cats, while thyroid-stimulating hormone was low in 16 of 16 cats. Most hyperthyroidism-chronic kidney disease cats (14 of 16) had total thyroxine greater than 30 nmol/l, whereas all the chronic kidney disease-only cats had total thyroxine less than 30 nmol/l. The combined measurement of free thyroxine with total thyroxine or thyroid-stimulating hormone may be of merit in the diagnosis of hyperthyroidism in cats with chronic kidney disease.

Feline focus: Diagnostic testing for feline thyroid disease: hypothyroidism.

PubMed

Peterson, Mark E

2013-08-01

Although naturally occurring hypothyroidism is very rare in cats, iatrogenic hypothyroidism is a recognized complication of treatment for hyperthyroidism. However, confirming the diagnosis of hypothyroidism in cats is not generally straightforward. The potential for false-negative and false-positive results exists with all thyroid function tests, especially in older cats that may have concurrent nonthyroidal illness. Therefore, all thyroid function test results must be interpreted in light of the cat's history, clinical signs, and other laboratory findings. If a low to low-normal serum thyroxine (T4) value is found in a cat that has been treated for hyperthyroidism, repeating the total T4 analysis, determining free T4 and thyroid stimulating hormone (TSH) concentrations, or performing a TSH stimulation test or thyroid scintigraphy may be needed to confirm the diagnosis.

Subclinical hyperthyroidism: possible danger of overzealous thyroxine replacement therapy.

PubMed

Ross, D S

1988-12-01

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

Diural TSH variations in hypothyroidism.

PubMed

Weeke, J; Laurberg, P

1976-07-01

There is a circadian variation in serum TSH in euthyroid subjects. A similar diurnal variation has been demonstrated in patients with hypothyroidism. In the present study the 24-hour pattern of serum TSH was investigated in eight patients with hypothyroidism of varying severity and in five hypothyroid patients treated with thyroxine (T4). There was a circadian variation in serum TSH in patients with hypothyroidism of moderate degree, and in patients treated for severe hypothyrodism with thyroxine. The pattern was similar to that found in normal subjects, i.e., low TSH levels in the daytime and higher levels at night. In severely hypothyroid patients, no diurnal variation in serum TSH was observed. A practical consequence is that blood samples for TSH measurements in patients with moderately elevated TSH levels are best taken after 1100 h, when the low day levels are reached.

Psychoneuroendocrine effects of combined thyroxine and triiodothyronine versus tyrosine during prolonged Antarctic residence.

PubMed

Palinkas, Lawrence A; Reedy, Kathleen R; Smith, Mark; Anghel, Mihai; Steel, Gary D; Reeves, Dennis; Shurtleff, David; Case, H Samuel; Van Do, Nhan; Reed, H Lester

2007-12-01

We previously reported that cognitive function improves with thyroxine and that there is a circannual pattern to mood and human TSH during Antarctic residence. To extend these findings, we examined the effects of tyrosine and a combined levothyroxine/liothyronine supplement in euthyroid men and women who spent the austral summer (n = 43) and/or winter (n = 42) in Antarctica. Randomized, placebo-controlled, clinical trial. Subjects were randomized to receive the following each day for 91.6 +/- 3.2 days in summer and/or 138.0 +/- 3.2 days in winter: (1) 12g tyrosine mixed in 113g applesauce; (2) 50 microg of levothyroxine and 12.5 microg of liothyronine (T4-T3 Supplement); or (3) placebo. Cognitive performance and mood were assessed using the Automatic Neuropsychological Assessment Metric - Isolated and Confined Environments. With placebo in summer, mood did not change while TSH decreased by 28%; in winter, there was a 136% degradation in mood (p < 0.01) and TSH increased by 18%. With combined T4-T3 supplement, there was a 51% degradation in mood in summer compared with placebo (p < 0.05) and TSH decreased by 57%; in winter there was a 135% degradation in mood while TSH was reduced by 26% (p < 0.05). Tyrosine use in summer was associated with no change in mood and a 30% decline in TSH, while in winter there was a 47% improvement in mood and TSH decreased by 28% along with a 6% increase in fT3 (p < 0.05). Administration of tyrosine leads to a significant reduction in serum TSH and improvement in mood in winter compared with placebo, while the combined T4-T3 supplement leads to a worsening of mood in summer and no improvement in winter. There appears to be a seasonal influence on the psychological response to interventions and the relationship to changes in TSH reductions.

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

PubMed

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

2017-05-01

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

High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase

PubMed Central

Wirth, Eva K.; Rijntjes, Eddy; Meyer, Franziska; Köhrle, Josef; Schweizer, Ulrich

2015-01-01

Background The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). Objective: To test the hypothesis that circulating low T4 and high T3 levels are caused by enhanced conversion of T4 via increased activity of hepatic type I deiodinase (Dio1). Methods We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Results Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Conclusions Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated. PMID:26601078

High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase.

PubMed

Wirth, Eva K; Rijntjes, Eddy; Meyer, Franziska; Köhrle, Josef; Schweizer, Ulrich

2015-09-01

The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). To test the hypothesis that circulating low T4 and high T3 levels are caused by enhanced conversion of T4 via increased activity of hepatic type I deiodinase (Dio1). We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated.

Congenital hypothyroidism in a kitten resulting in decreased IGF-I concentration and abnormal liver function tests.

PubMed

Quante, Saskia; Fracassi, Federico; Gorgas, Daniela; Kircher, Patrick R; Boretti, Felicitas S; Ohlerth, Stefanie; Reusch, Claudia E

2010-06-01

A 7-month-old male kitten was presented with chronic constipation and retarded growth. Clinical examination revealed disproportional dwarfism with mild skeletal abnormalities and a palpable thyroid gland. The presumptive diagnosis of congenital hypothyroidism was confirmed by low serum total thyroxine (tT(4)) concentration prior to and after the administration of thyroid stimulation hormone (TSH), increased endogenous TSH concentration and abnormal thyroid scintigraphic scan. The kitten had abnormal liver function tests and decreased insulin-like growth factor 1 (IGF-1) concentration, both of which returned to normal in correspondence with an improvement of the clinical signs after 6 weeks of thyroxine therapy. Congenital hypothyroidism is a rare disease that may present with considerable variation in clinical manifestation. In cases in which clinical signs are ambiguous, disorders such as portosystemic shunt and hyposomatotropism have to be taken into account as differential diagnosis. As hypothyroidism may be associated with abnormal liver function tests and low IGF-1 concentrations, test results have to be interpreted carefully. Copyright 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Hypothyroidism and Nephrotic Syndrome: Why, When and How to Treat.

PubMed

Mario, F Di; Pofi, R; Gigante, A; Rivoli, L; Rosato, E; Isidori, A M; Cianci, R; Barbano, B

2017-01-01

Hypothyroidism, characterised by low/normal free thyroxine (FT4) and free triiodothyronine (FT3) with elevated thyroid-stimulating hormone (TSH), is a well-known complication of nephrotic syndrome (NS). This is a common feature of primary and secondary glomerular diseases and comprises loss of protein in the urine and increased urinary excretion of thyroid hormones and thyroxine- binding globulin. With a normal thyroid reserve, this scenario is associated with the development of subclinical hypothyroidism, with a slight increase in TSH and normal free fractions. However, with a low thyroid reserve the transition toward overt hypothyroidism is almost inevitable, affecting morbidity and mortality. As T4 replacement is a cheap and well-established treatment to achieve a stable hormone status in different types of thyroid deficiency, it is essential to recognise and appropriately treat this condition. In this article we summarise the evidence on this nephro-endocrine disorder in humans and focus on diagnostic and therapeutic strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Influence of experimental hyperthyroidism on skeletal muscle metabolism in the rat.

PubMed

van Hardeveld, C; Kassenaar, A A

1977-05-01

In this study hind-limb perfusion was used to investigate the influence of thyroid hormones on some metabolic parameters in the skeletal muscle of the rat. Daily injection of 20 microng L-thyroxine (T4) per 100 g b. w. for a week caused a 25% increase in oxygen consumption. Further enlargement of the T4 dose had little additive effect. In the dose range 20--80 microng T4/100g b.w., no important changes occurred in lactate production or glucose consumption. Only at the highest T4 dose did the glucose consumption increase significantly. The most profound effect of T4 was on lipolysis. A daily dose of 20 microng T4/100 g b. w. gave a doubling of glycerol production rate, the maximum occuring at a dose of 40 microng T4/100 g b. w. Inactivation of the nervous system was without influence on the T4-induced increase in oxygen consumption. However, the T4-induced elevation of lipolysis disappeared after abolition of the nervous activity. This raises the possibility that the T4 effect on lipolysis in skeletal muscle is a potentiation of catecholamine effects. The T4-induced oxygen consumption increase might be dependent not on the lipolytic process but rather on other energy-consuming cell processes.

The dipeptidyl peptidase-4 inhibitor Saxagliptin improves function of circulating pro-angiogenic cells from type 2 diabetic patients

PubMed Central

2014-01-01

Background Type 2 diabetes (T2D) is associated with reduction and dysfunction of circulating pro-angiogenic cells (PACs). DPP-4 inhibitors, a class of oral agents for T2D, might possess pleiotropic vasculoprotective activities. Herein, we tested whether DPP-4 inhibition with Saxagliptin affects the function of circulating PACs from T2D and healthy subjects. Methods PACs were isolated from T2D (n = 20) and healthy (n = 20) subjects. Gene expression, clonogenesis, proliferation, adhesion, migration and tubulisation were assessed in vitro by incubating PACs with or without Saxagliptin and SDF-1α. Stimulation of angiogenesis by circulating cells from T2D patients treated with Saxagliptin or other non-incretinergic drugs was assessed in vivo using animal models. Results Soluble DPP-4 activity was predominant over cellular activity and was successfully inhibited by Saxagliptin. At baseline, T2D compared to healthy PACs contained less acLDL+Lectin+ cells, and showed altered expression of genes related to adhesion and cell cycle regulation. This was reflected by impaired adhesion and clonogenesis/proliferative response of T2D PACs. Saxagliptin + SDF-1α improved adhesion and tube sustaining capacity of PACs from T2D patients. CD14+ PACs were more responsive to Saxagliptin than CD14- PACs. While Saxagliptin modestly reduced angiogenesis by mature endothelial cells, circulating PACs-progeny cells from T2D patients on Saxagliptin treatment displayed higher growth factor-inducible in vivo angiogenetic activity, compared to cells from T2D patients on non-incretinergic regimen. Conclusions Saxagliptin reverses PACs dysfunction associated with T2D in vitro and improves inducible angiogenesis by circulating cells in vivo. These data add knowledge to the potential pleiotropic cardiovascular effects of DPP-4 inhibition. PMID:24886621

The dipeptidyl peptidase-4 inhibitor saxagliptin improves function of circulating pro-angiogenic cells from type 2 diabetic patients.

PubMed

Poncina, Nicol; Albiero, Mattia; Menegazzo, Lisa; Cappellari, Roberta; Avogaro, Angelo; Fadini, Gian Paolo

2014-05-14

Type 2 diabetes (T2D) is associated with reduction and dysfunction of circulating pro-angiogenic cells (PACs). DPP-4 inhibitors, a class of oral agents for T2D, might possess pleiotropic vasculoprotective activities. Herein, we tested whether DPP-4 inhibition with Saxagliptin affects the function of circulating PACs from T2D and healthy subjects. PACs were isolated from T2D (n = 20) and healthy (n = 20) subjects. Gene expression, clonogenesis, proliferation, adhesion, migration and tubulisation were assessed in vitro by incubating PACs with or without Saxagliptin and SDF-1α. Stimulation of angiogenesis by circulating cells from T2D patients treated with Saxagliptin or other non-incretinergic drugs was assessed in vivo using animal models. Soluble DPP-4 activity was predominant over cellular activity and was successfully inhibited by Saxagliptin. At baseline, T2D compared to healthy PACs contained less acLDL(+)Lectin(+) cells, and showed altered expression of genes related to adhesion and cell cycle regulation. This was reflected by impaired adhesion and clonogenesis/proliferative response of T2D PACs. Saxagliptin + SDF-1α improved adhesion and tube sustaining capacity of PACs from T2D patients. CD14+ PACs were more responsive to Saxagliptin than CD14- PACs. While Saxagliptin modestly reduced angiogenesis by mature endothelial cells, circulating PACs-progeny cells from T2D patients on Saxagliptin treatment displayed higher growth factor-inducible in vivo angiogenetic activity, compared to cells from T2D patients on non-incretinergic regimen. Saxagliptin reverses PACs dysfunction associated with T2D in vitro and improves inducible angiogenesis by circulating cells in vivo. These data add knowledge to the potential pleiotropic cardiovascular effects of DPP-4 inhibition.

Respiratory Syncytial Virus (RSV) Infects CD4+ T Cells: Frequency of Circulating CD4+ RSV+ T Cells as a Marker of Disease Severity in Young Children.

PubMed

Raiden, Silvina; Sananez, Inés; Remes-Lenicov, Federico; Pandolfi, Julieta; Romero, Cecilia; De Lillo, Leonardo; Ceballos, Ana; Geffner, Jorge; Arruvito, Lourdes

2017-04-01

Although human airway epithelial cells are the main target of respiratory syncytial virus (RSV), it also infects immune cells, such as macrophages and B cells. Whether T cells are permissive to RSV infection is unknown. We sought to analyze the permissiveness of CD4+ T cells to RSV infection. CD4+ and CD8+ T cells from cord blood, healthy young children, and adults were challenged by RSV or cocultured with infected HEp-2 cells. Infection, phenotype, and cytokine production by T cells were analyzed by flow cytometry or enzyme-linked immunosorbent assay. Expression of RSV antigens by circulating CD4+ T cells from infected children was analyzed by flow cytometry, and disease severity was defined by standard criteria. CD4+ and CD8+ T cells were productively infected by RSV. Infection decreased interleukin 2 and interferon γ production as well as the expression of CD25 and Ki-67 by activated CD4+ T cells. Respiratory syncytial virus antigens were detected in circulating CD4+ and CD8+ T cells during severe RSV infection of young children. Interestingly, the frequency of CD4+ RSV+ T cells positively correlated with disease severity. Respiratory syncytial virus infects CD4+ and CD8+ T cells and compromises T-cell function. The frequency of circulating CD4+ RSV+ T cells might represent a novel marker of severe infection. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

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 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

Thyroxine revisited.

PubMed

Katrusiak, Andrzej; Katrusiak, Anna

2004-12-01

The crystal structure of the common therapeutic agent, the pentahydrated sodium salt of L-thyroxine hormone (3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]-L-alanine), has been determined and discussed in relation to the drug's stability. The stoichiometry and absolute configuration (-)-C(8)S-[C15H10I4NO4]-.Na+.5H2O have been confirmed. The crystals are built of a three-dimensional supramolecular network with two symmetry-independent L-thyroxine anions, in two distinct conformations not previously reported, linked by strong NH-O hydrogen bonds into dimers. Two independent sodium cations are fivefold and sixfold coordinated. The cations and two independent water molecules not involved in coordinating the Na cations form sheets along the crystallographic (001) planes. The presence of differently coordinated cations and non-coordinating water molecules may be responsible for water transport and loss, for decay of the crystals, and subsequent low stability of the drug. Only a conglomerate could be obtained when racemic sodium thyroxine was crystallized from ethanol and methanol solutions by evaporation, which explains the equal penta-hydration of the sodium salts of enantiomorphic and racemic thyroxine, and the fact that there are no apparent differences in their stability. (c) 2004 Wiley-Liss, Inc. and the American Pharmacists Association

Evaluation of perturbations in serum thyroid hormones during human pregnancy due to dietary iodide and perchlorate exposure using a biologically based dose-response model.

PubMed

Lumen, Annie; Mattie, David R; Fisher, Jeffrey W

2013-06-01

A biologically based dose-response model (BBDR) for the hypothalamic pituitary thyroid (HPT) axis was developed in the near-term pregnant mother and fetus. This model was calibrated to predict serum levels of iodide, total thyroxine (T4), free thyroxine (fT4), and total triiodothyronine (T3) in the mother and fetus for a range of dietary iodide intake. The model was extended to describe perchlorate, an environmental and food contaminant, that competes with the sodium iodide symporter protein for thyroidal uptake of iodide. Using this mode-of-action framework, simulations were performed to determine the daily ingestion rates of perchlorate that would be associated with hypothyroxinemia or onset of hypothyroidism for varying iodide intake. Model simulations suggested that a maternal iodide intake of 75 to 250 µg/day and an environmentally relevant exposure of perchlorate (~0.1 µg/kg/day) did not result in hypothyroxinemia or hypothyroidism. For a daily iodide-sufficient intake of 200 µg/day, the dose of perchlorate required to reduce maternal fT4 levels to a hypothyroxinemic state was estimated at 32.2 µg/kg/day. As iodide intake was lowered to 75 µg/day, the model simulated daily perchlorate dose required to cause hypothyroxinemia was reduced by eightfold. Similarly, the perchlorate intake rates associated with the onset of subclinical hypothyroidism ranged from 54.8 to 21.5 µg/kg/day for daily iodide intake of 250-75 µg/day. This BBDR-HPT axis model for pregnancy provides an example of a novel public health assessment tool that may be expanded to address other endocrine-active chemicals found in food and the environment.

Evaluation of Thyroid Disorders During Head-and-Neck Radiotherapy by Using Functional Analysis and Ultrasonography

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

Bakhshandeh, Mohsen; Hashemi, Bijan, E-mail: bhashemi@modares.ac.ir; Mahdavi, Seyed Rabie

2012-05-01

Purpose: To evaluate thyroid function and vascular changes during radiotherapy for patients with head and neck cancer. Methods and Materials: Fifty patients treated with primary or postoperative radiotherapy for various cancers in the head and neck region were prospectively evaluated. The serum samples (triiodothyronine [T3], thyroxine [T4], thyroid-stimulating hormone [TSH], free triiodothyronine [FT3], and free thyroxine [FT4]), the echo level of the thyroid gland, and color Doppler ultrasonography (CDU) parameters of the right inferior thyroid artery (RITA) of the patients were measured before and at regular intervals during radiotherapy. The thyroid gland dose-volume histograms of the patients were derived frommore » their computed tomography-based treatment plans. Results: There was a significant fall in TSH level (p < 0.0001) but an increase in FT4 (p < 0.0001) and T4 (p < 0.022) levels during the radiotherapy course. The threshold dose required to produce significant changes was 12 Gy (Biologically Effective Dose in 2-Gy fractions, BED{sub 2}). There were significant rises in the patients' pulsatility index, resistive index, peak systolic velocity, blood volume flow levels, and RITA diameter (p < 0.0001), as detected by CDU during radiotherapy, compared to those parameters measured before the treatment. Hypoechogenicity and irregular echo patterns (p < 0.0001) were seen during radiotherapy compared to those before treatment. There was significant Pearson's correlation between the CDU parameters and T4, FT4, and TSH levels. Conclusions: Radiation-induced thyroiditis is regarded as primary damage to the thyroid gland. Thyroiditis can subsequently result in hypothyroidism or hyperthyroidism. Our results demonstrated that changes in thyroid vessels occur during radiotherapy delivered to patients. Vessel changes also can be attributed to the late effect of radiation on the thyroid gland. The hypoechogenicity and irregular echo patterns observed in patients may result from the increase in intrathyroidal flow.« less

Steady-State Serum T3 Concentrations for 48 Hours Following the Oral Administration of a Single Dose of 3,5,3'-Triiodothyronine Sulfate (T3S).

PubMed

Santini, Ferruccio; Giannetti, Monica; Ricco, Ilaria; Querci, Giorgia; Saponati, Giorgio; Bokor, Daniela; Rivolta, Giovanni; Bussi, Simona; Braverman, Lewis E; Vitti, Paolo; Pinchera, Aldo

2014-07-01

Sulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances their deiodination rate, leading to the generation of inactive metabolites. A desulfating pathway reverses this process, and thyromimetic effects have been observed following the parenteral administration of 3,5,3'-triiodothyronine (T3) sulfate (T3S) in rats. The present study investigated whether T3S is absorbed after oral administration in humans and if it represents a source of T3. Twenty-eight hypothyroid patients (7 men and 21 women; mean age, 44 ± 11 years) who had a thyroidectomy for thyroid carcinoma were enrolled. Replacement thyroid hormone therapy was withdrawn (42 days for thyroxine, 14 days for T3) prior to 131I remnant ablation. A single oral dose of 20, 40, 80 (4 patients/group), or 160 μg (16 patients/group) of T3S was administered 3 days before the planned administration of 131I. Blood samples for serum T3S and total T3 (TT3) concentrations were obtained at various times up to 48 hours after T3S administration. At all T3S doses, serum T3S concentrations increased, reaching a peak at 2 to 4 hours and progressively returning to basal levels within 8 to 24 hours. The T3S maximum concentration (Cmax) and area under the 0- to 48-hour concentration-time curve (AUC0-48h) were directly and significantly related to the administered dose. An increase in serum TT3 concentration was observed (significant after 1 hour), and the concentration increased further at 2 and 4 hours and then remained steady up to 48 hours after T3S administration. There was a significant direct correlation between the TT3 AUC0-48h and the administered dose of T3S. No changes in serum free thyroxine (T4) concentrations during the entire study period were observed, whereas serum thyroid-stimulating hormone levels increased slightly at 48 hours, but this was not related to the dose of T3S. No adverse events were reported. (1) T3S is absorbed following oral administration in hypothyroid humans; (2) after a single oral dose, T3S is converted to T3 in a dose-dependent manner, resulting in steady-state serum T3 concentrations for 48 hours; (3) T3S may represent a new agent in combination with T4 in the therapy of hypothyroidism, if similar conversion of T3S to T3 can be demonstrated in euthyroid patients who are already taking T4.

The administration of L-thyroxine as soft gel capsule or liquid solution.

PubMed

Vita, Roberto; Fallahi, Poupak; Antonelli, Alessandro; Benvenga, Salvatore

2014-07-01

Levothyroxine (l-T4) is the mainstay of treating hypothyroidism. The tablet is the traditional formulation of l-T4. Tablet l-T4 malabsorption results from either hindered gastric dissolution of the tablet or binding of l-T4 by sequestrants in the intestinal lumen. This review provides an overview of the pharmacokinetics of l-T4 formulations available in the market: the tablet, the soft gel capsule and the oral solution. We review literature on the new formulations and anticipate the areas of future research. Failure of l-T4 treatment to reach target serum thyroid-stimulating hormone levels generally prompts the physicians to increase l-T4 daily dose. In vitro studies have shown that the soft gel capsule releases the active ingredient more consistently at varying pH than the tablet. In addition, in vivo studies have confirmed the in vitro data and have demonstrated that both the soft gel capsule and the liquid formulation are capable to solve tablet l-T4 malabsorption caused by certain drugs, bariatric surgery or coffee. These new formulations may be attractive also for patients who cannot/do not want to change their (improper) habits of l-T4 ingestion. Finally, the oral solution l-T4 could be suitable for patients who cannot swallow the solid formulations.

Annual sex steroid and other physiological profiles of Pacific lampreys (Entosphenus tridentatus)

USGS Publications Warehouse

Mesa, Matthew G.; Bayer, Jennifer M.; Bryan, Mara B.; Sower, Stacia A.

2010-01-01

We documented changes in plasma levels of estradiol 17-β (E2), progesterone (P), 15α-hydroxytestosterone (15α-T), thyroxine (T4), triiodothyronine (T3), protein, triglycerides (TGs), and glucose in adult Pacific lampreys (Entosphenus tridentatus) held in the laboratory in two different years. Levels of E2 in both sexes ranged from 0.5 to 2 ng/mL from September to March, peaked in late April (2–4 ng/mL), and decreased in May, with levels higher in males than in females. Levels of P were low from September through April, but then increased substantially during May (2–4 ng/mL), with levels again highest in males. Levels of 15α-T in males were around 0.75 ng/mL through the winter before exceeding 1 ng/mL in April and decreasing thereafter, whereas females showed a gradual increase from 0.25 ng/mL in November to 0.5 ng/mL in April before decreasing. Thyroxine concentrations differed between fish in each year, with most having levels ranging from 0.75 to 2.5 ng/mL in the fall and winter, and only fish in 2003 showing distinct peaks (3–4 ng/mL) in early April or May. Plasma T3 was undetectable from November through mid-March before surging dramatically in April (ca. 150 ng/mL) and decreasing thereafter. Levels of protein, TGs, and glucose decreased or were stable during the fall and winter with TGs and glucose surging in late April to early May for some fish. Our study is the first to document long-term physiological changes in Pacific lampreys during overwintering and sexual maturation and increases our understanding of the life history of this unique fish.

Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2014-08-01

outcome. At 6 months post injury, patients will be screened for anterior pituitary function f the 61 mTBI subjects with IGF-1 results at the 6 month... anterior pituitary function, including somatomedin (IGF-1), thyroid stimulating hormone (TSH), thyroxine (Free T4), prolactin, and total cortisol in...resolution of PCS at six months after mTBI. We will also examine the incidence of single and multiple pituitary hormone deficiencies. The clinical

Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2013-08-01

injury, patients will be screened for anterior pituitary function of the 56 mTBI subjects with IGF-1 results, of the 63 who completed the 6 month... anterior pituitary function, including somatomedin (IGF -1 ), thyroid stimulating hormone (TSH), thyroxine (Free T4), prolactin, and total cortisol in all...resolution of PCS at six months after mTBI. We will also examine the incidence of single and multiple pituitary hormone deficiencies. The clinical

Effects of Long-Term Low-Level Radiofrequency Radiation Exposure on Rats. Volume 1. Design, Facilities, and Procedures.

DTIC Science & Technology

1983-09-01

uncovering unsuspected organ system malfunctions. In animals with subclinical or undiagnosed abnormalities, the emphasis is placed on the correct...normochromic, normocytic anemia are suggestive of hypothyroidism , although they do not occur in all hypothyroid animals. The thyroid hormones, thyroxine (T4...evaluation increased the opportunity to detect subclinical abnormalities and follow their pathophysiological course. Open-field assessment was conducted

Comparative evaluation of therapy with L-thyroxine versus no treatment in children with idiopathic and mild subclinical hypothyroidism.

PubMed

Wasniewska, Malgorzata; Corrias, Andrea; Aversa, Tommaso; Valenzise, Mariella; Mussa, Alessandro; De Martino, Lucia; Lombardo, Fortunato; De Luca, Filippo; Salerno, Mariacarolina

2012-01-01

The question of whether children with subclinical hypothyroidism (SH) should be treated or not is controversial due to the lack of studies on outcomes of SH children treated with L-thyroxine (L-T(4)) versus those receiving no therapy. (a) To evaluate thyroid tests under L-T(4) and after therapy withdrawal in 69 SH children (group A) and (b) to compare our results with those recorded in 92 untreated children (group B). Group A children were treated for 24 months and TSH and FT(4) levels 3 months after therapy withdrawal were compared with those measured in group B at the end of follow-up in order to investigate treatment effects. The prevalence of children who had normalized TSH at the end of follow-up was higher in group A, but the prevalence of those who had normalized or maintained unchanged TSH was similar in the two groups, as was the prevalence of children who exhibited a TSH increase >10 mU/l. In group A, TSH values at 27 months were associated with baseline values. (a) Two-year treatment in SH children is unable to modify posttherapy outcome of hyperthyrotropinemia; (b) therapy is unable to prevent the risk of further TSH increase after treatment withdrawal, and (c) posttherapy TSH outcome is conditioned by baseline TSH. Copyright © 2012 S. Karger AG, Basel.

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

PubMed

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

2014-08-01

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

Lymph node and circulating T cell characteristics are strongly correlated in end-stage renal disease patients, but highly differentiated T cells reside within the circulation.

PubMed

Dedeoglu, B; de Weerd, A E; Huang, L; Langerak, A W; Dor, F J; Klepper, M; Verschoor, W; Reijerkerk, D; Baan, C C; Litjens, N H R; Betjes, M G H

2017-05-01

Ageing is associated with changes in the peripheral T cell immune system, which can be influenced significantly by latent cytomegalovirus (CMV) infection. To what extent changes in circulating T cell populations correlate with T cell composition of the lymph node (LN) is unclear, but is crucial for a comprehensive understanding of the T cell system. T cells from peripheral blood (PB) and LN of end-stage renal disease patients were analysed for frequency of recent thymic emigrants using CD31 expression and T cell receptor excision circle content, relative telomere length and expression of differentiation markers. Compared with PB, LN contained relatively more CD4 + than CD8 + T cells (P < 0·001). The percentage of naive and central memory CD4 + and CD8 + T cells and thymic output parameters showed a strong linear correlation between PB and LN. Highly differentiated CD28 null T cells, being CD27 - , CD57 + or programmed death 1 (PD-1 + ), were found almost exclusively in the circulation but not in LN. An age-related decline in naive CD4 + and CD8 + T cell frequency was observed (P = 0·035 and P = 0·002, respectively) within LN, concomitant with an increase in central memory CD8 + T cells (P = 0·033). Latent CMV infection increased dramatically the frequency of circulating terminally differentiated T cells, but did not alter T cell composition and ageing parameters of LN significantly. Overall T cell composition and measures of thymic function in PB and LN are correlated strongly. However, highly differentiated CD28 null T cells, which may comprise a large part of circulating T cells in CMV-seropositive individuals, are found almost exclusively within the circulation. © 2017 British Society for Immunology.

Transporters for Antiretroviral Drugs in Colorectal CD4+ T Cells and Circulating α4β7 Integrin CD4+ T Cells: Implications for HIV Microbicides.

PubMed

Mukhopadhya, Indrani; Murray, Graeme I; Duncan, Linda; Yuecel, Raif; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

2016-09-06

CD4+ T lymphocytes in the colorectal mucosa are key in HIV-1 transmission and dissemination. As such they are also the primary target for antiretroviral (ARV)-based rectal microbicides for pre-exposure prophylaxis. Drug transporters expressed in mucosal CD4+ T cells determine ARV distribution across the cell membrane and, most likely, efficacy of microbicides. We describe transporters for antiretroviral drugs in colorectal mucosal CD4+ T lymphocytes and compare gene expression with circulating α4β7+CD4+ T cells, which traffic to the intestine and have been shown to be preferentially infected by HIV-1. Purified total CD4+ T cells were obtained from colorectal tissue and blood samples by magnetic separation. CD4+ T cells expressing α4β7 integrin were isolated by fluorescence-activated cell sorting from peripheral blood mononuclear cells of healthy volunteers. Expressions of 15 efflux and uptake drug transporter genes were quantified using Taqman qPCR assays. Expression of efflux transporters MRP3, MRP5, and BCRP and uptake transporter CNT2 were significantly higher in colorectal CD4+ T cells compared to circulating CD4+ T cells (p = 0.01-0.03). Conversely, circulating α4β7+CD4+ T cells demonstrated significantly higher expression of OATPD compared to colorectal CD4+ T cells (p = 0.001). To the best of our knowledge this is the first report of drug transporter gene expression in colorectal CD4+ and peripheral α4β7+CD4+ T cells. The qualitative and quantitative differences in drug transporter gene expression profiles between α4β7+CD4+ T cells and total mucosal CD4+ T cells may have significant implications for the efficacy of rectally delivered ARV-microbicides. Most notably, we have identified efflux drug transporters that could be targeted by selective inhibitors or beneficial drug-drug interactions to enhance intracellular accumulation of antiretroviral drugs.

2013 ETA Guideline: Management of Subclinical Hypothyroidism

PubMed Central

Pearce, Simon H.S.; Brabant, Georg; Duntas, Leonidas H.; Monzani, Fabio; Peeters, Robin P.; Razvi, Salman; Wemeau, Jean-Louis

2013-01-01

Subclinical hypothyroidism (SCH) should be considered in two categories according to the elevation in serum thyroid-stimulating hormone (TSH) level: mildly increased TSH levels (4.0-10.0 mU/l) and more severely increased TSH value (>10 mU/l). An initially raised serum TSH, with FT4 within reference range, should be investigated with a repeat measurement of both serum TSH and FT4, along with thyroid peroxidase antibodies, preferably after a 2- to 3-month interval. Even in the absence of symptoms, replacement therapy with L-thyroxine is recommended for younger patients (<65-70 years) with serum TSH >10 mU/l. In younger SCH patients (serum TSH <10 mU/l) with symptoms suggestive of hypothyroidism, a trial of L-thyroxine replacement therapy should be considered. For such patients who have been started on L-thyroxine for symptoms attributed to SCH, response to treatment should be reviewed 3 or 4 months after a serum TSH within reference range is reached. If there is no improvement in symptoms, L-thyroxine therapy should generally be stopped. Age-specific local reference ranges for serum TSH should be considered in order to establish a diagnosis of SCH in older people. The oldest old subjects (>80-85 years) with elevated serum TSH ≤10 mU/l should be carefully followed with a wait-and-see strategy, generally avoiding hormonal treatment. If the decision is to treat SCH, then oral L-thyroxine, administered daily, is the treatment of choice. The serum TSH should be re-checked 2 months after starting L-thyroxine therapy, and dosage adjustments made accordingly. The aim for most adults should be to reach a stable serum TSH in the lower half of the reference range (0.4-2.5 mU/l). Once patients with SCH are commenced on L-thyroxine treatment, then serum TSH should be monitored at least annually thereafter. PMID:24783053

Effects of T3 treatment on brown adipose tissue and energy expenditure in a patient with craniopharyngioma and hypothalamic obesity.

PubMed

van Santen, Hanneke M; Schouten-Meeteren, Antoinette Y; Serlie, Mireille; Meijneke, Ruud W H; van Trotsenburg, A S; Verberne, Hein; Holleman, Frits; Fliers, Eric

2015-01-01

Patients treated for childhood craniopharyngioma often develop hypothalamic obesity (HO), which has a huge impact on the physical condition and quality of life of these patients. Treatment for HO thus far has been disappointing, and although several different strategies have been attempted, all interventions had only transient effects. Since thyroid hormones increase energy expenditure metabolism (thyroid hormone induced thermogenesis), it was speculated that treatment with tri-iodothyronine (T3) may be beneficial. In 2002, a case report was published on reduction of body weight after T3 treatment for HO. No studies have been reported since. Recent experimental studies in rodents showed that T3 increases brown adipose tissue (BAT) activity via (pre)sympathetic pathways between the hypothalamus and BAT. Our aim was to investigate whether T3 treatment increases BAT activity in a patient with HO resulting from (treatment of) childhood craniopharyngioma. Thyroxine treatment for central hypothyroidism was switched to T3 monotherapy. Serum T3 and free thyroxine (FT4) concentrations were measured twice weekly for 2 months. ¹²³I-MIBG and ¹⁸F-FDG-PET after induction of non-shivering thermogenesis for the assessment of sympathetic and metabolic activity of BAT as well as indirect calorimetry for assessment of resting energy expenditure were performed before and during T3 treatment. No change in sympathetic and metabolic BAT activity, energy expenditure, or BMI was seen during T3 treatment despite the expected changes in thyroid hormone plasma concentrations. We conclude that T3 monotherapy does not seem to be effective in decreasing HO in childhood craniopharyngioma.

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

PubMed

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

2015-01-01

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

[Experiment research of Jiajian Yunvjian granules on hyperthyroidism graves].

PubMed

Guo, Juan; Chen, Changxun; Li, Xin

2009-09-01

To investigate the effects and the related mechanisms of Jiajian Yunujian (JJYNJ) granules, which were made from traditional Chinese medicinal prescription, on hyperthyroidism graves. Except that in the normal group, all mice were injected 350 mcirog x kg x d(-1) L-Thyroxin sodium to establish the hyperthyroidism graves model. The model mice were divided randomly into model control group, 3 different groups of JJYNJ granules at oral dosage of 2.17, 4.33, 8.66 g x kg(-1), every day and thiamazole group at oral dosage of 10 mg x kg(-1) every day, respectively. The body weight, heart/body weight index, heart rate (HR), spontaneous activity and oxygen consumption of all the mice were measured. The serum T3, T4 levels were evaluated with the method of RIA. Meanwhile, the effect of JJYNJ granules and thiamazole on iodine uptake by thyroid was determined by radio-assay. JJYNJ granules could improve the symptoms caused by thyroxin, increase body weight (P < 0.05), reduce heart/body weight index, spontaneous activity and oxygen consumption (P < 0.05). The HR of model group was (794.5 +/- 47.8) beats x min(-1), significantly faster than that of normal group (682.5 +/- 116.4) beats x min(-1). Those of low, middle and high JJYNJ granule group were (736.9 +/- 66.6), (742.1 +/- 62.3), (715.8 +/- 102.8) beats x min(-1) respectively, obviously slower than that of model group (P < 0.05). The serum T3, T4 levels of model group were (3.85 +/- 0.960), (234.46 +/- 58.11) microg x L(-1), significantly higher than those of normal group (0.99 +/- 0.30), (65.94 +/- 13.94) microg x L(-1), P < 0.01). Those of middle, high of JJYNJ granule group were (2.57 +/- 0.81), (164.27 +/- 72.63) microg x L(-1) and (2.70 +/- 0.55), (157.26 +/- 35.03) microg x L(-1). Those of thiamazole group were (2.88 +/- 0.59), (172.65 +/- 39.73) miicrog x L(-1). These values were significantly lower than those of model group. Thiamazole could significantly inhibit the iodine uptake in thyroid (P < 0.01), but JJYNJ granules did not block that obviously. JJYNJ granules could significantly improve the symptoms of experimental hyperthyroidism graves. Its mechanisms may be different from that of thiamazole, which is related to inhibiting the synthesis of thyroxin in thyroid.

Serum thyroxine concentrations following fixed-dose radioactive iodine treatment in hyperthyroid cats: 62 cases (1986-1989)

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

Meric, S.M.; Rubin, S.I.

The medical records of 62 hyperthyroid cats treated with a fixed dose of 4 mCi of radioactive iodine (131I) were reviewed. In 60 cats, serum thyroxine concentrations were determined after treatment, allowing evaluation of treatment success. Eighty-four percent of the cats had normal serum thyroxine concentrations after treatment. Five of the 60 cats (8%) remained hyperthyroxinemic after treatment. Five cats (8%) were hypothyroxinemic when evaluated within 60 days of treatment. Three of these cats had normal serum thyroxine concentrations 6 months after treatment, and none had clinical signs of hypothyroidism. The administration of a fixed dose of 4 mCi ofmore » 131I was determined to be an effective treatment for feline hyperthyroidism.« less

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

PubMed Central

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

2017-01-01

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

Effects of Arginase Inhibition in Hypertensive Hyperthyroid Rats.

PubMed

Rodríguez-Gómez, Isabel; Manuel Moreno, Juan; Jimenez, Rosario; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Wangensteen, Rosemary; Vargas, Félix

2015-12-01

This study analyzed the effects of chronic administration of N[omega]-hydroxy-nor-l-arginine (nor-NOHA), an inhibitor of arginase, on the hemodynamic, oxidative stress, morphologic, metabolic, and renal manifestations of hyperthyroidism in rats. Four groups of male Wistar rats were used: control, nor-NOHA-treated (10 mg/kg/day), thyroxine (T4)-treated (75 μg/rat/day), and thyroxine- plus nor-NOHA-treated rats. All treatments were maintained for 4 weeks. Body weight, tail systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, morphologic, metabolic, plasma, and renal variables were measured. Arginase I and II protein abundance and arginase activity were measured in aorta, heart, and kidney. The T4 group showed increased arginase I and II protein abundance, arginase activity, SBP, HR, plasma nitrates/nitrites (NOx), brainstem and urinary isoprostanes, proteinuria and cardiac and renal hypertrophy in comparison to control rats. In hyperthyroid rats, chronic nor-NOHA prevented the increase in SBP and HR and decreased proteinuria in association with an increase in plasma NOx and a decrease in brainstem and urinary isoprostanes. In normal rats, nor-NOHA treatment did not significantly change any hemodynamic, morphologic, or renal variables. Acute nor-NOHA administration did not affect renal or systemic hemodynamic variables in normal or T4-treated rats. Hyperthyroidism in rats is associated with the increased expression and activity of arginase in aorta, heart, and kidney. Chronic arginase inhibition with nor-NOHA suppresses the characteristic hemodynamic manifestations of hyperthyroidism in association with a reduced oxidative stress. These results indicate an important role for arginase pathway alterations in the cardiovascular and renal abnormalities of hyperthyroidism. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neonatal hyperthyroidism impairs epinephrine-provoked secretion of nerve growth factor and epidermal growth factor in mouse saliva.

PubMed

Lakshmanan, J; Landel, C P

1986-07-01

We examined long-term effects of neonatal hyperthyroidism on salivary secretions of nerve growth factor and epidermal growth factor in male and female mice at the age of 31 days. Hyperthyroidism was induced by thyroxine (T4) injections (0.4 microgram/g body weight/day) during days 0-6. Littermate control mice were treated with vehicle. T4 treatment did not alter the amounts of protein secreted into saliva but hormone administration induced alteration in the types of protein secreted. T4 treatment decreased the contents of both nerve growth factor and epidermal growth factor secreted into the saliva. A Sephadex G-200 column chromatographic profile revealed the presence of two distinct nerve growth factor immunoreactive peaks, while epidermal growth factor immunoreactivity predominantly eluted as a single low molecular weight form. T4 treatment did not alter the molecular nature of their secretion, but the treatment decreased their contents. These results indicate an impairment in salivary secretion of nerve growth factor and epidermal growth factor long after T4 treatment has been discontinued.

Thyroid hormone disruption and cognitive impairment in rats exposed to PBDE during postnatal development.

PubMed

de-Miranda, Andressa S; Kuriyama, Sergio N; da-Silva, Camille S; do-Nascimento, Monicke S C; Parente, Thiago E M; Paumgartten, Francisco J R

2016-08-01

Polybrominated diphenyl ether flame-retardants (PBDEs) are thyroid-disrupting environmental chemicals. We investigated the effects of postnatal exposure to DE-71 (a mixture of tetra- and penta-brominated congeners), n-propylthiouracil (PTU) and thyroxine (T4) replacement on open-field (OF) and radial maze (RAM) tests. Wistar rats (5 males/5 females per litter, 32 litters) were treated orally (PND 5-22) with PTU (4mg/kg bw/d), DE-71 (30mg/kg bw/d), with and without co-administration of T4 (15μg/kg bw/d, sc). PTU depressed T4 serum levels and body weight gain and enlarged thyroid gland. Although decreasing T4 levels, DE-71 did not change thyroid and body weights. PTU-treated rats showed hyperactivity (PND 42 and 70), and working and reference memory learning deficits (RAM, PND 100). Although not altering motor activity and working memory, DE-71 caused a reference memory deficit (females only). T4 co-administration averted hypothyroxinemia and long-term cognitive deficits caused by PTU and DE-71. Copyright © 2016 Elsevier Inc. All rights reserved.

Autonomic contribution to the blood pressure and heart rate variability changes in early experimental hyperthyroidism.

PubMed

Safa-Tisseront, V; Ponchon, P; Laude, D; Elghozi, J L

1998-12-01

To study the interaction between autonomic nervous activity and thyroid hormones in the control of heart rate (HR) and blood pressure (BP). Thyrotoxicosis was produced by injections of L-thyroxine (0.5 mg/kg/day for five days). Blockers were atropine (0.5 mg/kg), atenolol (1 mg/kg) or prazosin (1 mg/kg). Eight animals were studied in each group. Spectral analyses was performed using continuous BP time series obtained in conscious rats. Thyroxine treatment was sufficient to induce a significant degree of tachycardia (423+/-6 vs 353+/-4 bpm, P < 0.001, unpaired Student's t test), systolic BP elevation (142+/-3 vs 127+/-2 mmHg, P < 0.001) and cardiac hypertrophy (1.165+/-0.017 vs 1.006+/-0.012 g, P < 0.001). The intrinsic HR was markedly increased after treatment with thyroxine (497+/-16 vs 373+/-10 bpm, P < 0.05). Vagal tone was positively linearly related to intrinsic HR (r = 0.84, P< 0.01). Atenolol neither modified HR nor BP variability in rats with hyperthyroidism. The thyrotoxicosis was associated with a reduction of the 0.4 Hz component of BP variability (modulus 1.10+/-0.07 vs 1.41+/-0.06 mmHg, P < 0.01). Prazosin was without effect on this 0.4 Hz component in hyperthyroid animals. These data show a functional diminution of the vascular and cardiac sympathetic tone in early experimental hyperthyroidism. The marked rise in the intrinsic HR could be the main determinant of tachycardia. The BP elevation may reflexly induce vagal activation and sympathetic (vascular and cardiac) inhibition.

Lake Roosevelt Fisheries Monitoring Program; Measurement of Thyroxin Concentration as an Indicator of the Critical Period for Imprinting in the Kokanee Salmon (Orcorhynchus Nerka) Implications for Operating Lake Roosevelt Kokanee Hatcheries; 1991 Supplement Report.

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

Scholz, Allan T.; White, Ronald J.; Koehler, Valerie A.

1992-05-01

Previous investigations have determined that thyroid hormone surges activate olfactory imprinting in anadromous salmonid smolts. The mechanism of action appears to require binding of thyroid hormones to receptors in brain cell nuclei, which stimulates neuron differentiation and wires a pattern of neuron circuitry that allows for the permanent storage of the imprinted olfactory memory. In this study, thyroxine concentrations [T{sub 4}] were measured in 487 Lake Whatcom stock and 70 Lake Roosevelt stock Kokanee salmon to indicate the critical period for imprinting. Eggs, alevins and fry, reared at the Spokane Indian Kokanee Hatchery, were collected from January through August 1991.more » Sampled fish were flash frozen on dry ice and stored at {minus}80{degrees}C until T{sub 4} was extracted and concentrations determined by radioimmunassay. Mean concentration {+-} SEM of 10--20 individual fish (assayed in duplicate) were determined for each time period. T{sub 4} concentration peaked on the day of hatch at 16.8 ng/g body weight and again at swim-up at 16.0 {+-} 4.7 ng/g body weight. T{sub 4} concentration was 12.5 to 12.9 ng/g body weight in eggs, 7.1 to 15.2 ng/g body weight in. alevins, 4.5 to 11.4 ng/g body weight in 42 to 105 day old fry and 0.1 to 2.9 ng/g body weight in 112 to 185 day old fry. T{sub 4} concentrations were highest in eggs at 13.3 {+-} 2.8 ng/g body weight, then steadily decreased to 0.1 {+-} 0.1 ng/g body weight in older fry. Fry were released in Lake Roosevelt tributaries in July and August 1991, at about 170--180 days post hatching, in order to imprint them to those sites. The results of this study indicate that the time of release was not appropriate for imprinting. If T{sub 4} levels are an accurate guide for imprinting in kokanee, our results suggest that the critical period for imprinting in kokanee is at hatching or swim-up stages.« less

Assessment of a method for measuring serum thyroxine by radioimmunoassay, with use of polyethylene glycol precipitation. [/sup 125/I tracer technique

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

Farid, N.R.; Kennedy, C.

We assessed the efficacy of a new thyroxine radioimmunoassay kit (Abbott) in which polyethylene glycol is used to separate bound from free hormone. Mean serum thyroxine was 88 +- 15 (+-SD) ..mu..g/liter for 96 normal persons. Results for hypothyroid and hyperthyroid persons were clearly separated from those for normal individuals. Women taking oral contraceptive preparations showed variable increases in their serum thyroxine values. The coefficient of variation ranged from 1 to 3% within assay and from 5.4 to 11% among different assays. Excellent parallelism was demonstrated between thyroxine values estimated by this method and those obtained either by competitive proteinmore » binding or by a separate radioimmunoassay for the hormone.« less

Metabolism of thyroxine in Rana catesbeiana tadpoles during metamorphic climax

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

Galton, V.A.; Munck, K.

1981-01-01

Previous studies have indicated that premetamorphic tadpoles do not convert T4 to T3 to a measurable extent (1). The present study was performed to determine whether a T4 5'-monodeiodinating system is acquired at later stages of development. (/sup 125/I)T4 metabolism in vivo was determined in tadpoles at most stages of prometamorphosis and metamorphic climax and, for comparison, in premetamorphic tadpoles. The conversion of (/sup 125/I)T4 to (/sup 125/I)T3, as indicated by the presence of an /sup 125/I-labeled product in serum and liver preparations that cochromatographed with carrier T3, was sometimes observed in tadpoles near the end of prometamorphosis and wasmore » always evident in tadpoles that were either undergoing or had completed metamorphic climax. However, during this phase, no correlation could be drawn between the extent of T3 production and morphological development. The formation of T3 from T4 in vivo was significantly decreased in tadpoles pretreated with propylthiouracil. The T45'-monodeiodinating system could be induced in premetamorphic tadpoles by injecting them with either T4 or T3. This finding together with the observation that normal acquisition of this system occurs at the time when endogenous T4 and T3 levels are rising rapidly suggest that its development is under the control of the thyroid hormones.« less

Hyperthyroidism enhances 5-HT-induced contraction of the rat pulmonary artery: role of calcium-activated chloride channel activation.

PubMed

Oriowo, Mabayoje A; Oommen, Elsie; Khan, Islam

2011-11-01

Experimentally-induced hyperthyroidism in rodents is associated with signs and symptoms of pulmonary hypertension. The main objective of the present study was to investigate the effect of thyroxine-induced pulmonary hypertension on the contractile response of the pulmonary artery to 5-HT and the possible underlying signaling pathway. 5-HT concentration-dependently contracted artery segments from control and thyroxine-treated rats with pD(2) values of 5.04 ± 0.19 and 5.34 ± 0.14, respectively. The maximum response was significantly greater in artery segments from thyroxine-treated rats. Neither BW 723C86 (5-HT(2B)-receptor agonist) nor CP 93129 (5-HT(1B)-receptor agonist) contracted ring segments of the pulmonary artery from control and thyroxine-treated rats at concentrations up to 10(-4)M. There was no significant difference in the level of expression of 5-HT(2A)-receptor protein between the two groups. Ketanserin (3 × 10(-8)M) produced a rightward shift of the concentration-response curve to 5-HT in both groups with equal potency (-logK(B) values were 8.1 ± 0.2 and 7.9 ± 0.1 in control and thyroxine-treated rats, respectively). Nifedipine (10(-6)M) inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. The calcium-activated chloride channel blocker, niflumic acid (10(-4)M) also inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. It was concluded that hyperthyroidism enhanced 5-HT-induced contractions of the rat pulmonary artery by a mechanism involving increased activity of calcium-activated chloride channels. Copyright © 2011 Elsevier B.V. All rights reserved.

Expression of TIGIT and FCRL3 is Altered in T Cells from Patients with Distinct Patterns of Chronic Autoimmune Thyroiditis.

PubMed

Štefanić, Mario; Tokić, Stana; Suver-Stević, Mirjana; Glavaš-Obrovac, Ljubica

2018-06-11

Co-inhibitory receptors (IR), such as TIGIT and FCRL3, provide a checkpoint against highly destructive immune responses. Co-expression of TIGIT and FCRL3, in particular, has been linked to the HELIOS + subset of regulatory CD4 + FOXP3 + T-cells. Of these, CD4 + FOXP3-exon(E)2 + cells have higher expression of IR and exhibit strongest suppressive properties. Nevertheless, how the expression of TIGIT, FCRL3, HELIOS, and FOXP3E2 is regulated in chronic autoimmune thyroiditis (AT), is not known. Thirty patients with AT [encompassing spontaneously euthyroid (euAT), hypothyroid-untreated and L-thyroxine-treated cases)] and 10 healthy controls (HC) were recruited. FCRL3, TIGIT, HELIOS and FOXP3E2 mRNA expression levels in peripheral blood (PB) T cells were measured via quantitative real-time PCR and compared to clinicopathological factors. The TIGIT and FCRL3 expression levels from T cells of AT cases were inversely related to the thyroid volume, and were significantly increased in hypothyroid patients (on+off L-thyroxine), but not euAT cases. The FCRL3 expression in PB T cells positively correlated with thyroid-peroxidase autoantibody levels; by contrast, T cells from aged AT patients and combined samples (AT+HC) accumulated more TIGIT mRNA. The patients with higher TIGIT mRNA levels had a greater prevalence of hypothyroidism, showing higher peak thyrotropin levels at diagnosis or at follow-up. Multiple IR, namely FCRL3 and TIGIT, but not the transcription factors HELIOS and FOXP3E2, showed increased mRNA levels in PB T cells from end-stage, long-standing and/or more aggressive AT, in proportion to disease severity. A relation with major clinical subphenotypes was observed, thereby identifying IR as potentially important players in AT. © Georg Thieme Verlag KG Stuttgart · New York.

Severe rhabdomyolysis and acute renal failure in an adolescent with hypothyroidism.

PubMed

Comak, Elif; Koyun, Mustafa; Kiliçarslan-Akkaya, Bahar; Bircan, Iffet; Akman, Sema

2011-01-01

Hypothyroidism has been reported rarely as the cause of rhabdomyolysis in adults and children. We present here a non-compliant adolescent with a diagnosis of hypothyroidism who developed rhabdomyolysis and acute renal failure with no additional predisposing factor. A 13-year-old girl with a previous history of hypothyroidism due to thyroid hypoplasia presented with generalized myalgia, malaise, vomiting, and oliguria lasting for three days. Neurological examination revealed bilateral marked weakness and tenderness of muscles of both lower and upper extremities. Urine had bloody appearance and urine analysis showed blood reaction with dipstick test, but there were no erythrocytes on microscopic examination. Serum creatine phosphokinase and myoglobin levels were elevated. Thyroid stimulating hormone (TSH) levels were high, and free thyroxine (T4) and triiodothyronine (T3) levels were low, compatible with uncontrolled hypothyroidism. Renal function tests showed acute renal failure. Other causes of rhabdomyolysis such as muscular trauma, drugs, toxins, infections, vigorous exercise, and electrolyte abnormalities were excluded. Hemodialysis was administered for 24 sessions. After L-thyroxine therapy, thyroid function tests normalized, muscle strength improved, serum muscle enzyme levels returned to normal levels, and renal function tests recovered. One must be aware that rhabdomyolysis may develop in a non-compliant patient with hypothyroidism.

Thyroid hormones in chronic heat exposed men

NASA Astrophysics Data System (ADS)

Gertner, A.; Israeli, R.; Lev, A.; Cassuto, Y.

1983-03-01

Previous reports have indicated that thyroid gland activity, is depressed in the heat. Total thyroxine (T4) and triiodothyronine (T3) serum levels in 17 workers of the metal work shop at a plant near the Dead Sea and 8 workers in Beer Sheva, Israel were examined. The metal workshop of the plant near the Dead Sea is part of a large chemical plant. The one in Beer Sheva is part of a large construction company. Maintenance work, as well as metal work projects are performed in both workshops. During the work shifts, the workers of the Dead Sea plant were exposed to temperatures ranging from 30 36°C (May Oct.) and 14 21°C (Dec. Feb). In Beer Sheva the range was 25 32°C (June Sept.) and 10 17°C (Dec. Feb.). Total T4 was measured by competitive protein binding and total T3 by radioimmunoassay in blood drawn before work (0700) in July and January. In summer. T4 was higher and T3 was lower for both groups than in winter. The observed summer T3 decrease may result from depressed extrathyroidal conversion of T4 to T3. We conclude that the regulation of energy metabolism in hot climates may be related to extrathyroidal conversion of T4 to T3.

Insulin-like growth factor-binding protein-3 (IGFBP-3) but not insulin-like growth factor-I (IGF-I) remains elevated in euthyroid TSH-suppressed Graves' disease.

PubMed

Wan Nazaimoon, W M; Khalid, B A

1998-04-01

Thyroid hormones have been shown to be involved in the regulation of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) expression. This is a cross-sectional study to look at the effects of thyroid hormone status on the circulating levels of IGF-I and IGFBP-3 in a group of 127 patients, aged 20-80 years, who were hyperthyroid, hypothyroid, rendered euthyroid and clinically euthyroid with normal free thyroxine (fT4), but suppressed thyroid stimulating hormone (TSH) levels. TSH was measured by the IMx (Abbott) ultrasensitive assay, while radioimmunoassays for total T3 and T4 were performed using kits from ICN, USA; fT4 and fT3 using kits from DPC USA; IGF-I and IGFBP-3 using kits from Nichols Institute Diagnostics B.V., Netherlands. Differences in the levels of IGF-I between the 4 groups of patients were significant only in the patients aged 20-40. Mean (+/-SEM) IGF-I levels of hypothyroid patients (169+/-19ng/ml) was significantly lower than hyperthyroid (315+/-26 ng/ml, p=0.003), euthyroid patients (241+/-19 ng/ml, p=0.002) and patients with suppressed TSH (308+/-29 ng/ml, p=0.02). The IGF-I levels of the hyperthyroid and suppressed TSH patients were, however, comparable to age-matched normal subjects (281+/-86 ng/ml). Although there was no difference in mean IGFBP-3 levels between the 4 groups of patients, the levels in the patients aged 20-40 with hyperthyroidism (3.7+/-0.9 microg/ml) and suppressed TSH (3.9+/-1.2 microg/ml) were significantly higher (p=0.02) than age-matched normal subjects (3.1+/-0.8 microg/ml). The IGF-I levels of the thyroid patients aged 20-40 showed significant negative correlation to TSH and positive correlations to the thyroid hormones. Hence, whilst low IGF-I is associated with hypothyroidism, high IGFBP-3 is associated with hyperthyroidism. Our finding that IGFBP-3 remained significantly elevated in patients with suppressed TSH but normalised fT4 and fT3 is important as it suggests a prolonged tissue effect of thyroid hormones on IFGBP-3. As such patients have been shown to have higher risk for atrial fibrillation, the significance and possible role of IGFBP-3 in these conditions should be further elucidated in future studies.

Disruptive effects of persistent organohalogen contaminants on thyroid function in white whales (Delphinapterus leucas) from Svalbard.

PubMed

Villanger, G D; Lydersen, C; Kovacs, K M; Lie, E; Skaare, J U; Jenssen, B M

2011-06-01

We analysed levels of 56 organohalogen contaminants (OHCs) including brominated flame retardants, polychlorinated biphenyls (PCBs), and organochlorine pesticides in the blubber of white (beluga) whales (Delphinapterus leucas) from Svalbard, Norway (N=12; 6 adults [5 males and 1 female] and 6 subadults [4 males and 2 females]) collected in 1996-2001. We also measured circulating levels of thyroid hormones (THs) and thyroid stimulating hormone (TSH) in the whales. The results confirm that OHC levels in these white whales are among the highest levels recorded in wildlife from Svalbard, and at the high end of the range when compared to white whales from the North American Arctic. A projection to latent structure (PLS) model (subadults and adult males grouped together) revealed that known or suspected thyroid disruptive contaminants (polybrominated diphenylether [PBDE]-28, -47, -99, -100, and -154, hexachlorobenzene [HCB], and PCB-105) were negatively correlated with circulating levels of total thyroxin (TT4), free T4 (FT4) and free triiodothyronine (FT3). Most of these negative relationships were also confirmed using partial correlations controlling for length (and thus age) of the whales. The positive correlations of TT4, FT4 and FT3 with hexabromocyclododecane (HBCD), α-hexachlorocyclohexane (α-HCH), chlorinated bornanes CHB-40 and CHB-62 revealed by the PLS model were not confirmed by partial correlations. TH levels in the present study appeared to be somewhat lower than levels measured in beluga whales from the Canadian Arctic. However, we were not able to determine if this was caused by different levels of OHCs, or differences in biological factors (e.g. age, sex, moulting status, and season) and analytical methods between the studies. Although the sample sizes were low and statistical models cannot depict the biological cause-effect relationships, this study suggests negative influences of specific OHCs, particularly PBDEs, on thyroid hormone levels in white whales. The impact this might have on individual and population health is unknown. Copyright © 2011 Elsevier B.V. All rights reserved.

Thyroid and adrenal cortical rhythmicity during bed rest.

NASA Technical Reports Server (NTRS)

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

1972-01-01

The effects of prolonged bed rest on adrenocortical and thyroid function were assessed in eight healthy males, aged 20-40 years, who were submitted to bed rest for 56 days on a 14L:10D regimen (lights-on, 9:00 AM). Four of these subjects exercised three times daily throughout the experiment. Circulating cortisol, triiodothyronine, and thyroxine, concentrations were determined in blood samples drawn at four hourly intervals for 48-hr periods before, 10, 20, 30, 42, and 54 days during, and 10 days post-bed rest. Significant fluctuations in the circulating levels of all three hormones occurred with peaks at 7:30 AM. The suggestion is advanced that thyroid rhythms may be posture dependent.

Sex steroid levels, oocyte maturation and spawning performance in Waigieu seaperch (Psammoperca waigiensis) exposed to thyroxin, human chorionic gonadotropin, luteinizing hormone releasing hormone and carp pituitary extract.

PubMed

Pham, Hung Quoc; Nguyen, Anh Tuong; Nguyen, Mao Dinh; Arukwe, Augustine

2010-02-01

In the present study, we have investigated the sex steroid hormone levels, oocyte maturation and spawning performance in Waigieu seaperch (Psammoperca waigiensis) exposed to different doses (0, (control), 0.05, 0.25 and 0.5 mg/kg fish) of thyroxin (T(4)) both through diet (continuously) and injection (single injection). In addition, we also studied plasma steroid hormone levels and spawning performances in female fish injected with a single dose of D-Ala(6), Pro(9)-Net-mGnRH (LHRHa: 50 microg/kg), human chronic gonadotropin (HCG: 1,500 IU/kg) and carp pituitary extract (CPE: 10 mg/kg). In all experiments, samples were collected at 0, 6, 12, 24 and 48 h after exposure. T4 exposure via dietary route produced differential and enhanced effects, compared with when the compound was injected to the broodstock. A significant association between exposure to dietary T4, elevated plasma steroid hormone levels, maturation-, spawning-, fertilization- and hatching rate, egg diameter, embryogenesis and larval growth were observed. Interestingly, we observed that broodstock groups fed with T4 doses spawned 20 days earlier than the control group. Thus, we propose that these differences may be attributed to higher systemic availability of T4 due to dietary exposure that is easily transferable to eggs and embryos, as opposed to injection that require absorption to increase bioavailability. Furthermore, our results show that LHRHa, CPE and HCG produced significant increase in spawning rate, but significantly reduced fertilization- and hatching rates. Waigieu seaperch is a new candidate for marine aquaculture in Vietnam and relatively little is known about the reproductive biology and endocrinology of this species. Therefore, the present study forms an integral basis for understanding the reproductive endocrinology of a tropical marine finfish with increasing aquaculture prospects and may also contribute in the development of sustainable aquaculture of this species in a developing country such as Vietnam. 2009 Elsevier Inc. All rights reserved.

Does exposure to phthalates influence thyroid function and growth hormone homeostasis? The Taiwan Environmental Survey for Toxicants (TEST) 2013.

PubMed

Huang, Han-Bin; Pan, Wen-Harn; Chang, Jung-Wei; Chiang, Hung-Che; Guo, Yue Leon; Jaakkola, Jouni J K; Huang, Po-Chin

2017-02-01

Previous epidemiologic and toxicological studies provide some inconsistent evidence that exposure to phthalates may affect thyroid function and growth hormone homeostasis. To assess the relations between exposure to phthalates and indicators of thyroid function and growth hormone homeostasis disturbances both among adults and minors. We conducted a population-based cross-sectional study of 279 Taiwanese adults (≥18 years old) and 79 minors (<18 years old) in 2013. Exposure assessment was based on urinary biomarkers, 11 phthalate metabolites measured by using online liquid chromatography/tandem mass spectrometry. Indicators of thyroid function included serum levels of thyroxine (T 4 ), free T 4 , triiodothyronine, thyroid-stimulating hormone, and thyroxine-binding globulin (TBG). Growth hormone homeostasis was measured as the serum levels of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3). We applied multivariate linear regression models to examine these associations after adjusting for covariates. Among adults, serum T 4 levels were negatively associated with urinary mono-(2-ethyl-5-hydroxyhexyl) phthalate (β=-0.028, P=0.043) and the sum of urinary di-(2-ethylhexyl) phthalate (DEHP) metabolite (β=-0.045, P=0.017) levels. Free T 4 levels were negatively associated with urinary mono-ethylhexyl phthalate (MEHP) (β=-0.013, P=0.042) and mono-(2-ethyl-5-oxohexyl) phthalate (β=-0.030, P=0.003) levels, but positively associated with urinary monoethyl phthalate (β=0.014, P=0.037) after adjustment for age, BMI, gender, urinary creatinine levels, and TBG levels. Postive associations between urinary MEHP levels and IGF-1 levels (β=0.033, P=0.006) were observed. Among minors, free T 4 was positively associated with urinary mono benzyl phthalate levels (β=0.044, P=0.001), and IGF-1 levels were negatively associated with the sum of urinary DEHP metabolite levels (β=-0.166, P=0.041) after adjustment for significant covariance and IGFBP3. Our results are consistent with the hypothesis that exposure to phthalates influences thyroid function and growth hormone homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Osteoporotic cytokines and bone metabolism on rats with induced hyperthyroidism; changes as a result of reversal to euthyroidism.

PubMed

Simsek, Gönül; Karter, Yesari; Aydin, Seval; Uzun, Hafize

2003-12-31

Hyperthyroidism is characterized by increased bone turnover and resorptive activity. Raised levels of serum osteoporotic cytokines, such as interleukin (IL) -1beta, IL-6 and tumor necrosis factor (TNF)-alpha have been demonstrated previously in hyperthyroidism. These elevations are controversial and it is difficult to differentiate the contribution of thyroid hormones to the elevation of cytokines from that of the autoimmune inflammation in Graves' disease (GD) and follicular cell damage in thyroiditis. Therefore, we investigated the effect of thyroid hormones on serum IL-1beta, IL-6, TNF-alpha levels and bone metabolism on L-thyroxine induced hyperthyroid rats and changes in cytokine levels and bone metabolism on the same rats after reversal to euthyroidism. Rats were treated with L-thyroxine for 5 weeks (0.4 mg/ 100 g food). Plasma T3, T4, TSH and serum IL-1beta, IL-6, TNFalpha, Calcium (Ca), phosphorous (P), parathyroid hormone (PTH), alkaline phosphatase (ALP), bone alkaline phosphatase (B-ALP) levels were measured and differential leucocyte counts were made initially, at the 5th week of the experiment (hyperthyroid state) and 5 weeks after quitting the administration of L-thyroxine (euthyroid state). Significant rises in serum IL-1beta, IL-6 and TNFalpha were noted in hyperthyroidism (P < 0.001). In euthyroid state, IL-15, IL-6 and TNFalpha decreased significantly, but IL-beta and TNFalpha were significantly higher than the baseline values (P < 0.05) while IL-6 levels turned back to the baseline values. Plasma T3 and T4 levels were significantly correlated with serum cytokines in hyperthyroid state while there was no correlation in euthyroid states. Ca and P levels did not differ significantly while PTH levels declined significantly in the hyperthyroid state (P < 0.05). After the reversal to the euthyroidism, there was no significant change in Ca, P and PTH levels. ALP and B-ALP increased significantly in hyperthyroidism (P < 0.001, P < 0.01) and they did not decrease in euthyroid state. The lymphocyte number and ratio in differentials increased significantly in the hyperthyroid state (P < 0.001). In euthyroidism they decreased significantly (P < 0.001) but it was significantly higher than the baseline value (P < 0.05). Our findings showed that the deleterious effect on bone metabolism in hyperthyroidism might be mediated by cytokines and the increased bone turnover in hyperthyroidism failed to decrease despite euthyroidism.

Effect of PFDA on Cardiac Membrane Function.

DTIC Science & Technology

1983-03-01

NO. 3. RECIPIENT’S CATALOG NUMBER AFOS-TR - / .... 4. TITLE (and Subtitle) 5. TVPF nF REPORT & PERIOD COVERED EFFECT OF PFDA ON CARDIAC MEMBRANE...Continue on reverse side II necessary and Identify by block number) Heart, Thyroxine, Triiodothyronine, PFDA 0t C) 20, ABSTRACT (Continue on revereD...eide If neceesary and Identify by block number) LTJ "Yihe in vivo and in vitro heart rates of rats treated with 75 mg/kg PFDA was __j significantly

Endocrine effects of 2,2{prime},4,4{prime}-tetrachlorobiphenyl in the African clawed frog (Xenopus laevis)

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

Diana, S.; Hansen, L.; Foley, G.

1995-12-31

Ortho-substituted polychlorinated biphenyls are known to exhibit estrogenic activity and, in some cases, to enhance excretion of tetraiodothyronine (T4), resulting in hypothyroxinemia in mammals. Since thyroxine activity is essential for amphibian metamorphosis, and amphibian sex determination can be altered or reversed by exposure to exogenous estrogens or androgens, the effects of exposure of larvae of the African clawed frog (Xenopus laevis) to 2,2{prime},4,4{prime}-tetrachlorobiphenyl (CB 47) were investigated. Eggs and larvae of X. laevis were exposed to nominal concentrations of CB 47 of 0.05 or 0.25 ppm (1 ppm was found to result in 100% mortality) throughout the period of larvalmore » development, and effects on rates of metamorphosis and body growth and on gonad morphology were determined. Stage of metamorphosis, body length and body weight did not differ between treatment and control groups, following exposure to these sub-lethal concentrations, at any time during larval development. Effects of exposure on gonad morphology will be discussed. The failure of CB 47 to delay or prevent metamorphosis under these conditions may be due to poor responsiveness of hepatic UDP-glucuronyl transferases to induction, or novel systems of thyroxine and/or PCB transport, metabolism and excretion in larval amphibians.« less

Development studies of Aurelia (jellyfish) ephyrae which developed during the SLS-1 mission

NASA Technical Reports Server (NTRS)

Spangenberg, D. B.; Jernigan, T.; Mccombs, R.; Lowe, B. T.; Sampson, M.; Slusser, J.

1994-01-01

Aurelia polyps (scyphistomae) and ephyrae were exposed to microgravity for nine days aboard the space shuttle during the SLS-1 mission. During strobilation, polyps segment transversely and each segment develops into an ephyra. Polyps were induced to strobilate at 28 C, using iodine or thyroxine, at L(Launch)-48h, L-24h, and L+8h. Ephyrae developed in the groups tested in space and on Earth. The number of ephyrae formed per polyp was slightly higher in the L+8h groups as compared with those induced at L-24h and L-48h. On Earth, iodine is used by jellyfish to synthesize jellyfish-thyroxine (Jf T(sub 4)), needed for ephyra production. Since iodine-treated polyps strobilated and formed ephyrae in space, it appears that jellyfish can synthesize Jf-T(sub 4) in space. Indeed, two groups of polyps not given inducer formed ephryae in space, presumably due to enhanced Jf-T(sub 4) synthesis, utilization or accumulation. Some ephyrae that formed in space were also fixed in space on Mission Day (MD) 8; others were fixed post-flight. Examination of living ephyrae with the light microscope and fixed ones with the Scanning and Transmission Electron Microscopes revealed that those which developed in space were morphologically very similar to those which developed on Earth. Quantitation of arm numbers determined that there were no significant differences between space and Earth-developed ephyrae. Pulsing abnormalities, however, were found in greater number (18.3%) in space-developed ephyrae than in Earth-developed controls (2.9%). These abnormalities suggest abnormal development of the graviceptors, the neuromuscular system, or a defect in the integration between these systems in apparently microgravity-sensitive animals.

A mode of action for induction of thyroid gland tumors by Pyrethrins in the rat

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

Finch, John M.; Osimitz, Thomas G.; Gabriel, Karl L.

2006-08-01

Prolonged treatment with high doses of Pyrethrins results in thyroid gland tumors in the rat. To elucidate the mode of action for tumor formation, the effect of Pyrethrins on rat thyroid gland, thyroid hormone levels and hepatic thyroxine UDPglucuronosyltransferase activity was investigated. Male Sprague-Dawley CD rats were fed diets containing 0 (control) and 8000 ppm Pyrethrins and female rats diets containing 0, 100, 3000 and 8000 ppm Pyrethrins for periods of 7, 14 and 42 days and for 42 days followed by 42 days of reversal. As a positive control, rats were also fed diets containing 1200-1558 ppm sodium Phenobarbitalmore » (NaPB) for 7 and 14 days. The treatment of male rats with 8000 ppm Pyrethrins, female rats with 3000 and 8000 ppm Pyrethrins and both sexes with NaPB resulted in increased thyroid gland weights, which were associated with follicular cell hypertrophy. Thyroid follicular cell replicative DNA synthesis was increased by treatment with Pyrethrins and NaPB for 7 and/or 14 days. Treatment with Pyrethrins and NaPB increased hepatic microsomal thyroxine UDPglucuronosyltransferase activity and serum thyroid stimulating hormone levels (TSH), but reduced serum levels of either thyroxine (T{sub 4}) and/or triiodothyronine (T{sub 3}). The effects of Pyrethrins in female rats were dose-dependent, with 100 ppm being a no-effect level, and on cessation of treatment were essentially reversible in both sexes. The concordance between the effects of Pyrethrins and NaPB suggests that the mode of action for Pyrethrins-induced rat thyroid gland tumors is similar to that of some other non-genotoxic inducers of hepatic xenobiotic metabolism.« less

Congenital hypothyroidism treatment in infants: a comparative study between liquid and tablet formulations of levothyroxine.

PubMed

Peroni, Elena; Vigone, Maria Cristina; Mora, Stefano; Bassi, Lorenzo Andrea; Pozzi, Clara; Passoni, Arianna; Weber, Giovanna

2014-01-01

To compare the effects of liquid and tablet formulations of levothyroxine (L-T4) in 78 newborns with congenital hypothyroidism (CH). 39 patients received liquid L-T4 (group A) and 39 patients received tablets (group B). Thyroid-stimulating hormone (TSH) and free thyroxine (fT4) were measured and L-T4 dose recorded at onset of therapy and during the first year of treatment. Developmental quotient (DQ) was assessed by Griffiths' mental development scales at 12 months of age. Gestational age, birth weight, screening TSH, etiology and severity of CH, age at onset of therapy and median initial L-T4 dose were similar in both groups. fT4 concentration normalized before 10 days of treatment in all patients. Normalization of TSH concentration was achieved after 7-10 days of therapy in 87% of group A patients and in 82% of group B patients. Group A patients had significantly lower TSH values compared with those of group B at 7-10 days (p = 0.05) and 6-8 months (p = 0.043) of treatment, despite similar L-T4 dose and fT4 concentration. Mean DQ scores were within normal range in all patients. We confirmed the efficacy and safety of both formulations. The TSH inhibition trend when using liquid L-T4 may be linked to a higher absorption in comparison to the tablets.

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.

Mercury exposure associated with altered plasma thyroid hormones in the declining western pond turtle (Emys marmorata) from California mountain streams.

PubMed

Meyer, Erik; Eagles-Smith, Collin A; Sparling, Donald; Blumenshine, Steve

2014-01-01

Mercury (Hg) is a global threat to wildlife health that can impair many physiological processes. Mercury has well-documented endocrine activity; however, little work on the effects of Hg on the thyroid hormones triiodothyronine (T3) and thyroxine (T4) in aquatic wildlife exists despite the fact that it is a sensitive endpoint of contaminant exposure. An emerging body of evidence points to the toxicological susceptibility of aquatic reptiles to Hg exposure. We examined the endocrine disrupting potential of Hg in the western pond turtle (Emys marmorata), a long-lived reptile that is in decline throughout California and the Pacific Northwest. We measured total Hg (THg) concentrations in red blood cells (RBCs) and plasma T3 and T4 of turtles from several locations in California that have been impacted by historic gold mining. Across all turtles from all sites, the geometric mean and standard error THg concentration was 0.805 ± 0.025 μg/g dry weight. Sampling region and mass were the strongest determinants of RBC THg. Relationships between RBC THg and T3 and T4 were consistent with Hg-induced disruption of T4 deiodination, a mechanism of toxicity that may cause excess T4 levels and depressed concentrations of biologically active T3.

Mercury exposure associated with altered plasma thyroid hormones in the declining western pond turtle (Emys marmorata) from California mountain streams

USGS Publications Warehouse

Meyer, Erik; Eagles-Smith, Collin A.; Sparling, Donald; Blumenshine, Steve

2014-01-01

Mercury (Hg) is a global threat to wildlife health that can impair many physiological processes. Mercury has well-documented endocrine activity; however, little work on the effects of Hg on the thyroid hormones triiodothyronine (T3) and thyroxine (T4) in aquatic wildlife exists despite the fact that it is a sensitive endpoint of contaminant exposure. An emerging body of evidence points to the toxicological susceptibility of aquatic reptiles to Hg exposure. We examined the endocrine disrupting potential of Hg in the western pond turtle (Emys marmorata), a long-lived reptile that is in decline throughout California and the Pacific Northwest. We measured total Hg (THg) concentrations in red blood cells (RBCs) and plasma T3 and T4 of turtles from several locations in California that have been impacted by historic gold mining. Across all turtles from all sites, the geometric mean and standard error THg concentration was 0.805 ± 0.025 μg/g dry weight. Sampling region and mass were the strongest determinants of RBC THg. Relationships between RBC THg and T3 and T4 were consistent with Hg-induced disruption of T4 deiodination, a mechanism of toxicity that may cause excess T4 levels and depressed concentrations of biologically active T3.

Thyroid function in 36 dogs with leishmaniosis due to Leishmania infantum before and during treatment with allopurinol with or without meglumine antimonate.

PubMed

Saridomichelakis, Manolis N; Xenoulis, Panagiotis G; Chatzis, Manolis K; Kasabalis, Dimitris; Steiner, Jörg M; Suchodolski, Jan S; Petanides, Theodoros

2013-10-18

Hypothyroidism may predispose to the development of canine leishmaniosis or it may appear during the course of the latter due to infiltration and destruction of the thyroid gland by infected macrophages. The main purpose of this study was to evaluate thyroid function through measurement of serum total thyroxin (tT₄), free thyroxin (fT₄), and canine thyroid stimulating hormone (cTSH) concentrations in 36 dogs with leishmaniosis, before and after 2 and 4 weeks of treatment with allopurinol with or without meglumine antimonate. Before treatment 27/36 (75%) dogs had serum tT₄ concentrations below the lower limit of the reference interval but only 2 of them had concurrently serum fT₄ concentrations below the lower limit of the reference interval and none had increased serum cTSH concentrations. During treatment there were no significant changes in serum tT₄ or fT₄ concentrations, whereas a significant increase in serum cTSH was observed. Two dogs had decreased serum tT₄ and fT₄ but normal cTSH concentrations before treatment and two other dogs had decreased serum tT₄ and increased cTSH, but normal fT₄ concentrations during the treatment period. Although hypothyroidism could not be definitively excluded in these dogs it is considered unlikely based on their overall hormonal profile, clinical presentation, and response to treatment. Therefore, hypothyroidism does not appear to be an important predisposing disease or a frequent complication of canine leishmaniosis. Copyright © 2013 Elsevier B.V. All rights reserved.

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

PubMed

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

2014-08-01

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

Induction and prevention of low-T3 syndrome in exercising women.

PubMed

Loucks, A B; Callister, R

1993-05-01

To investigate the influence of exercise on thyroid metabolism, 46 healthy young regularly menstruating sedentary women were randomly assigned to a 3 x 2 experimental design of aerobic exercise and energy availability treatments. Energy availability was defined as dietary energy intake minus energy expenditure during exercise. After 4 days of treatments, low energy availability (8 vs. 30 kcal.kg body wt-1.day-1) had reduced 3,5,3'-triiodothyronine (T3) by 15% and free T3 (fT3) by 18% and had increased thyroxine (T4) by 7% and reverse T3 (rT3) by 24% (all P < 0.01), whereas free T4 (fT4) was unchanged (P = 0.08). Exercise quantity (0 vs. 1,300 kcal/day) and intensity (40 vs. 70% of aerobic capacity) did not affect any thyroid hormone (all P > 0.10). That is, low-T3 syndrome was induced by the energy cost of exercise and was prevented in exercising women by increasing dietary energy intake. Selective observation of low-T3 syndrome in amenorrheic and not in regularly menstruating athletes suggests that exercise may compromise the availability of energy for reproductive function in humans. If so, athletic amenorrhea might be prevented or reversed through dietary reform without reducing exercise quantity or intensity.

Circulating rotavirus-specific T cells have a poor functional profile.

PubMed

Parra, Miguel; Herrera, Daniel; Jácome, María Fernanda; Mesa, Martha C; Rodríguez, Luz-Stella; Guzmán, Carolina; Angel, Juana; Franco, Manuel A

2014-11-01

Frequencies of circulating T cells producing IFN-γ, TNF-α, and IL-2, and percentages of T cells proliferating after stimulation with rotavirus (RV), tetanus toxoid, and influenza were evaluated in PBMC derived from healthy adults and children. In addition, the potential anergic state of RV-specific T cells was analyzed by stimulation of PBMC with RV antigen in the presence of three anergy inhibitors (rIL-2, rIL-12, or DGKα-i). The quality and magnitude of RV-T cell responses were significantly lower than those of tetanus toxoid and influenza antigens. RV-CD4 T cell response was enriched in monofunctional IFN-γ(+) cells, while influenza-CD4 and tetanus toxoid-CD4 T cell responses were enriched in multifunctional T cells. Moreover, rIL-2--unlike rIL-12 or DGKα-i--increased the frequencies of RV-CD4 TNF-α(+), CD4 IFN-γ(+), and CD8 IFN-γ(+) cells. Thus, circulating RV-T cells seem to have a relatively poor functional profile that may be partially reversed in vitro by the addition of rIL-2. Copyright © 2014 Elsevier Inc. All rights reserved.

Circulating CD4+CXCR5+ T cells contribute to proinflammatory responses in multiple ways in coronary artery disease.

PubMed

Ding, Ru; Gao, Wenwu; He, Zhiqing; Wu, Feng; Chu, Yang; Wu, Jie; Ma, Lan; Liang, Chun

2017-11-01

Coronary artery disease (CAD) is a common subtype of cardiovascular disease. The major contributing event is atherosclerosis, which is a progressive inflammatory condition resulting in the thickening of the arterial wall and the formation of atheromatous plaques. Recent evidence suggests that circulating CD4 + CXCR5 + T cells can contribute to inflammatory reactions. In this study, the frequency, phenotype, and function of circulating CD4 + CXCR5 + T cells in CAD patients were examined. Data showed that circulating CD4 + CXCR5 + T cells in CAD patients were enriched with a PD-1 + CCR7 - subset, which was previously identified as the most potent in B cell help. The CD4 + CXCR5 + T cells in CAD patients also secreted significantly higher levels of IFN-γ, IL-17A, and IL-21 than those from healthy controls. Depleting the PD-1 + population significantly reduced the cytokine secretion. Interestingly, the CD4 + CXCR5 + PD-1 - T cells significantly upregulated PD-1 following anti-CD3/CD28 or SEB stimulation. CD4 + CXCR5 + T cells from CAD patients also demonstrated more potent capacity to stimulate B cell inflammation than those from healthy individuals. The phosphorylation of STAT1 and STAT3 were significantly higher in B cells incubated with CD4 + CXCR5 + T cells from CAD than controls. The IL-6 and IFN-γ expression were also significantly higher in B cells incubated with CD4 + CXCR5 + T cells from CAD. Together, this study demonstrated that CAD patients presented a highly activated CD4 + CXCR5 + T cell subset that could contribute to proinflammatory responses in multiple ways. The possibility of using CD4 + CXCR5 + T cells as a therapeutic target should therefore be examined in CAD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

The effects of clobazam treatment in rats on the expression of genes and proteins encoding glucronosyltransferase 1A/2B (UGT1A/2B) and multidrug resistance‐associated protein-2 (MRP2), and development of thyroid follicular cell hypertrophy

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

Miyawaki, Izuru, E-mail: izuru-miyawaki@ds-pharma.co.jp; Tamura, Akitoshi; Matsumoto, Izumi

Clobazam (CLB) is known to increase hepatobiliary thyroxine (T4) clearance in Sprague–Dawley (SD) rats, which results in hypothyroidism followed by thyroid follicular cell hypertrophy. However, the mechanism of the acceleration of T4-clearance has not been fully investigated. In the present study, we tried to clarify the roles of hepatic UDP-glucronosyltransferase (UGT) isoenzymes (UGT1A and UGT2B) and efflux transporter (multidrug resistance–associated protein-2; MRP2) in the CLB-induced acceleration of T4-clearance using two mutant rat strains, UGT1A-deficient mutant (Gunn) and MRP2-deficient mutant (EHBR) rats, especially focusing on thyroid morphology, levels of circulating hormones (T4 and triiodothyronine (T3)) and thyroid-stimulating hormone (TSH), and mRNAmore » or protein expressions of UGTs (Ugt1a1, Ugt1a6, and Ugt2b1/2) and MRP2 (Mrp). CLB induced thyroid morphological changes with increases in TSH in SD and Gunn rats, but not in EHBR rats. T4 was slightly decreased in SD and Gunn rats, and T3 was decreased in Gunn rats, whereas these hormones were maintained in EHBR rats. Hepatic Ugt1a1, Ugt1a6, Ugt2b1/2, and Mrp2 mRNAs were upregulated in SD rats. In Gunn rats, UGT1A mRNAs (Ugt1a1/6) and protein levels were quite low, but UGT2B mRNAs (Ugt2b1/2) and protein were prominently upregulated. In SD and Gunn rats, MRP2 mRNA and protein were upregulated to the same degree. These results suggest that MRP2 is an important contributor in development of the thyroid cellular hypertrophy in CLB-treated rats, and that UGT1A and UGT2B work in concert with MRP2 in the presence of MRP2 function to enable the effective elimination of thyroid hormones. -- Highlights: ► Role of UGT and MRP2 in thyroid pathology was investigated in clobazam-treated rats. ► Clobazam induced thyroid cellular hypertrophy in SD and Gunn rats, but not EHBR rats. ► Hepatic Mrp2 gene and protein were upregulated in SD and Gunn rats, but not EHBR rats. ► Neither serum thyroid hormones (T3/T4) nor thyroid pathology changed in EHBR rats. ► Mrp2 was implied to be a key molecule in clobazam-induced thyroid pathology in rats.« less

Luteal Expression of Thyroid Hormone Receptors During Gestation and Postpartum in the Rat

PubMed Central

Navas, Paola B.; Redondo, Analía L.; Cuello-Carrión, F. Darío; Roig, Laura M. Vargas; Valdez, Susana R.; Jahn, Graciela A.

2014-01-01

Background: Progesterone (P4) is the main steroid secreted by the corpora lutea (CL) and is required for successful implantation and maintenance of pregnancy. Although adequate circulating levels of thyroid hormone (TH) are needed to support formation and maintenance of CL during pregnancy, TH signaling had not been described in this gland. We determined luteal thyroid hormone receptor isoforms (TR) expression and regulation throughout pregnancy and under the influence of thyroid status, and in vitro effects of triiodothyronine (T3) exposure on luteal P4 synthesis. Methods: Euthyroid female Wistar rats were sacrificed by decapitation on gestational day (G) 5, G10, G15, G19, or G21 of pregnancy or on day 2 postpartum (L2). Hyperthyroidism and hypothyroidism were induced in female Wistar rats by daily administration of thyroxine (T4; 0.25 mg/kg subcutaneously) or 6-propyl-2-thiouracil (PTU; 0.1 g/L in drinking water), respectively. Luteal TR expression of mRNA was determined using real-time reverse-transcription quantitative polymerase chain reaction, and of protein using Western blot and immunohistochemistry. Primary cultures of luteal cells and of luteinized granulosa cells were used to study in vitro effects of T3 on P4 synthesis. In addition, the effect of T3 on P4 synthesis under basal conditions and under stimulation with luteinizing hormone (LH), prolactin (PRL), and prostaglandin E2 (PGE2) was evaluated. Results: TRα1, TRα2, and TRβ1 mRNA were present in CL, increasing during the first half and decreasing during the second half of pregnancy. At the protein level, TRβ1 was abundantly expressed during gestation reaching a peak at G19 and decreasing afterwards. TRα1 was barely expressed during early gestation, peaked at G19, and diminished thereafter. Expression of TRβ1 and TRα1 at the protein and mRNA level were not influenced by thyroid status. T3 neither modified P4 secretion from CL of pregnancy nor its synthesis in luteinized granulosa cells in culture. Conclusions: This study confirms for the first time the presence of TR isoforms in the CL during pregnancy and postpartum, identifying this gland as a TH target during gestation. TR expression is modulated in this tissue in accordance with the regulation of P4 metabolism, and the abrupt peripartum changes suggest a role of TH during luteolysis. However, TH actions on the CL do not seem to be related to a direct regulation of P4 synthesis. PMID:24684177

Impaired circulating CD4+ LAP+ regulatory T cells in patients with acute coronary syndrome and its mechanistic study.

PubMed

Zhu, Zheng-Feng; Meng, Kai; Zhong, Yu-Cheng; Qi, Liang; Mao, Xiao-Bo; Yu, Kun-Wu; Zhang, Wei; Zhu, Peng-Fei; Ren, Ze-Peng; Wu, Bang-Wei; Ji, Qin-Wei; Wang, Xiang; Zeng, Qiu-Tang

2014-01-01

CD4(+) latency-associated peptide (LAP)(+) regulatory T cells (Tregs) are a newly discovered T cell subset in humans and the role of these cells in patients with acute coronary syndrome (ACS) has not been explored. We designed to investigate whether circulating frequency and function of CD4(+)LAP(+) Tregs are defective in ACS. One hundred eleven ACS patients (acute myocardial infarction and unstable angina) and 117 control patients were enrolled in the study. The control patients consisted of chronic stable angina (CSA) and chest pain syndrome (CPS). The frequencies of circulating CD4(+)LAP(+) Tregs and the expression of the transmembrane protein glycoprotein-A repetitions predominant (GARP) on CD4(+) T cells were determined by flow cytometry. The function of CD4(+)LAP(+) Tregs was detected using thymidine uptake. Serum interleukin-10 (IL-10) and transforming growth factor-β protein (TGF-β) levels were detected using ELISA and expression of GARP mRNA in peripheral blood mononuclear cells (PBMCs) was measured by real time-polymerase chain reaction. We found ACS patients had a significantly lower frequency of circulating CD4(+)LAP(+) Tregs, and the function of these cells was reduced compared to controls. The expression of GARP in CD4(+) T cells and the serum levels of TGF-β in ACS patients were lower than those of control patients. The serum levels of IL-10 were similar between the two cohorts. A novel regulatory T cell subset, defined as CD4(+)LAP(+) T cells is defective in ACS patients.

Ethylene thiourea: thyroid function in two groups of exposed workers.

PubMed Central

Smith, D M

1984-01-01

Ethylene thiourea is manufactured at one factory in the United Kingdom and is mixed into masterbatch rubber at another. Clinical examinations and thyroid function tests were carried out over a period of three years on eight process workers and five mixers and on matched controls. The results show that the exposed mixers, but not exposed process workers, have significantly lower levels of total thyroxine (T4) than the controls. One mixer had an appreciably raised level of thyroid stimulation hormone (TSH). PMID:6743584

Ethylene thiourea: thyroid function in two groups of exposed workers.

PubMed

Smith, D M

1984-08-01

Ethylene thiourea is manufactured at one factory in the United Kingdom and is mixed into masterbatch rubber at another. Clinical examinations and thyroid function tests were carried out over a period of three years on eight process workers and five mixers and on matched controls. The results show that the exposed mixers, but not exposed process workers, have significantly lower levels of total thyroxine (T4) than the controls. One mixer had an appreciably raised level of thyroid stimulation hormone (TSH).

[The effect of synchronization on estrus and pregnancy in sheep and on levels of thyroxine, triiodothyronine, 17 beta-estradiol, progesterone and cholesterol].

PubMed

Bekeová, E; Krajnicáková, M; Hendrichovský, V; Maracek, I

1991-07-01

Knowledge of pathogenesis of sexual dysfunctions at altered thyroid activity is limited by the knowledge of multiple and ubiquitous action of its hormones throughout the organism. One of the possibilities of modulatory influence of thyroid hormones on sexual functions can be realized through the participation of thyroxine and triiodothyronine in the synthesis and metabolism of primary substrate of steroid synthesis--cholesterol. The presented work is aimed at the study of simultaneous dynamic changes of concentrations of thyroxine (T4), triiodothyronine (T3), 17 beta-estradiol (E2), progesterone (P4) and cholesterol (Chol) during synchronization of the rutting period and gravidity at parallel correlative evaluation of mutual relations of the followed parameters in ten Merino sheep in the seasonal period. Synchronization was achieved by chlorsuperlutin (Agelin--vaginal swabs, Spofa; 20 mg of chlorsuperlutin/swab) and PMSG (500 I. U./animal). Blood was sampled by means of a jugular vein puncture at the time of swab insertion (-13th day) and after three (-10th day) and seven (-7th day) following days, at the removal of swabs and application of PMSG (-3rd day), on the day of insemination (zero day), on the 7th, 14th and 17th day and in the middle of the 2nd, 3rd, 4th and 5th month of gravidity. In the phase of oestrus synchronization a significant increase of E2 concentrations on days -7 and -3 of the experiment (0.47 +/- 0.079 and 0.542 +/- 0.177 nmol.l-1 of serum, P less than 0.001; P less than 0.001) was observed compared to the E2 values on day -13 (0.084 +/- 0.036 nmol.l-1 of serum). Parallel to these observations, marked intermittent changes of T4 (Tab. I, Graph 1) were recorded with the lowest values of this parameter observed on days -10 (41.75 +/- 20.23, P less than 0.05) and -3 (50.22 +/- 18.77, P less than 0.05) and the highest on day -7 (96.77 +/- 17.51 nmol.l-1, P less than 0.01) and day zero (85.40 +/- 19.59 nmol.l-1 of serum, P less than 0.05) in comparison with the -13th day (67.22 +/- 18.29 nmol.l-1 of serum). Concentrations of P4 (Tab. I, Graph 4) declined to the lowest values on day zero observation (0.09 +/- 0.08 nmol.l-1 of serum, P less than 0.05 vs 3.40 +/- 3.61 nmol.l-1 on day -13). No significant changes of concentrations of T3 (Tab. I, Graph 2) and Chol (Tab. I, Graph 5) were observed during oestrus synchronization. During gravidity, concentrations of E2 (Tab. I Graph 3) showed an increasing trend compared to the -13th day.(ABSTRACT TRUNCATED AT 250 WORDS)

Examining the relationship between brominated flame retardants (BFR) exposure and changes of thyroid hormone levels around e-waste dismantling sites.

PubMed

Wang, Hongmei; Zhang, Yuan; Liu, Qian; Wang, Feifei; Nie, Jing; Qian, Yan

2010-09-01

Brominated flame retardants (BFRs) released from e-waste related activities may affect the health of local people. Assessing the impact of e-waste exposure during recycling and dismantling activities on local people's thyroid hormone levels is an area of ongoing research. During November and December 2008, the process of e-waste recycling and dismantling was investigated, and 236 occupation-exposed people and 89 non-occupation-exposed people approximate to the e-waste recycling sites were surveyed; their thyroid hormone levels (THs), thyrotropins (TSH) and BFRs levels in serum were assayed. Multiple regression models were constructed to analyze the changes of serum THs and TSH in the people living in the exposure area (exposure group) and the people in the control group. Covariates known to be or likely to be associated with THs, TSH and BFRs levels were analyzed. Lower level of Triiodothyronine (T(3)) in both occupation-exposed and non-occupation-exposed group were observed (p<0.01), when compared with the control group, and the same trend was obtained for free triiodothyronine (fT(3)) and free thyroxine (fT4) (p<0.01). However, no significant difference in thyroxine (T(4)) was found between the two groups. The level of TSH in the e-waste recycling occupational-exposed group ranged from 0.00 to 5.00microIU/ml with a mean of 1.26microIU/ml, whereas the level of TSH in the control group was from 0.03 to 5.54microIU/ml with a mean of 1.57microIU/ml. This study revealed that people having worked on e-waste recycling and dismantling had significantly lower TSH compared with the control group (p<0.01). Moreover, the level of BDE-205 is positively associated with the level of T4, as confirmed by the linear regression model (unstandardized regression coefficient, beta=0.25, rho=0.001) and a weaker positive relation was also found between the levels of BDE-126 and T4. Meanwhile, a weak negative relation was found between the levels of PBB 103 and T3, and between the levels of fT3 and fT4. These results suggest that exposure to BFRs released from primitive e-waste handling may contribute to the changes of THs and TSH levels. Crown Copyright 2010. Published by Elsevier GmbH. All rights reserved.

Hyperthyrotropinemia in newly diagnosed cystic fibrosis patients with pancreatic insufficiency reversed by enzyme therapy.

PubMed

Giannakopoulos, Aris; Katelaris, Anni; Noni, Maria; Karakonstantakis, Theodore; Kanaka-Gantenbein, Christina; Doudounakis, Stavros

2018-05-01

Patients with cystic fibrosis (CF) commonly present with an elevated TSH concentration, suggesting subclinical hypothyroidism. Its relation to concomitant pancreatic insufficiency and its natural course upon initiation of enzyme replacement have not been adequately studied. Herein, we investigated the thyroid function in newly diagnosed infants with CF and monitored the course of thyroid function response to pancreatic enzyme substitution treatment. Fourteen, newly diagnosed infants with CF and pancreatic insufficiency, were followed every 6-8 weeks for 6 months ensuing onset of pancreatic enzyme substitution therapy. All infants had normal TSH values on neonatal screening. Ten out of 14 (71%) had hyperthyrotropinemia and normal freeT4 values at presentation. No patient received thyroxine. Upon follow-up, after 6 months, TSH values normalized in 90% of infants with CF and hyperthyrotropinemia. Serum selenium levels were negatively correlated with TSH levels. Mild TSH elevation is a frequent finding in newly diagnosed cystic fibrosis patients with pancreatic insufficiency during infancy. TSH elevation resolves in most cases after initiation of enzyme substitution and improvement of nutritional status without any substitutive therapy with thyroxine. What is Known: • Newly diagnosed infants with cystic fibrosis often present with a state of hyperthyrotropinemia suggesting subclinical hypothyroidism. What is New: • Pancreatic enzyme substitution and improvement of nutrition restores normal TSH levels without the need of thyroxine therapy.

Exogenous thyrotoxicosis in dogs attributable to consumption of all-meat commercial dog food or treats containing excessive thyroid hormone: 14 cases (2008-2013).

PubMed

Broome, Michael R; Peterson, Mark E; Kemppainen, Robert J; Parker, Valerie J; Richter, Keith P

2015-01-01

To describe findings in dogs with exogenous thyrotoxicosis attributable to consumption of commercially available dog foods or treats containing high concentrations of thyroid hormone. Retrospective and prospective case series. 14 dogs. Medical records were retrospectively searched to identify dogs with exogenous thyrotoxicosis attributable to dietary intake. One case was found, and subsequent cases were identified prospectively. Serum thyroid hormone concentrations were evaluated before and after feeding meat-based products suspected to contain excessive thyroid hormone was discontinued. Scintigraphy was performed to evaluate thyroid tissue in 13 of 14 dogs before and 1 of 13 dogs after discontinuation of suspect foods or treats. Seven samples of 5 commercially available products fed to 6 affected dogs were analyzed for thyroxine concentration; results were subjectively compared with findings for 10 other commercial foods and 6 beef muscle or liver samples. Total serum thyroxine concentrations were high (median, 8.8 μg/dL; range, 4.65 to 17.4 μg/dL) in all dogs at initial evaluation; scintigraphy revealed subjectively decreased thyroid gland radionuclide in 13 of 13 dogs examined. At ≥ 4 weeks after feeding of suspect food or treats was discontinued, total thyroxine concentrations were within the reference range for all dogs and signs associated with thyrotoxicosis, if present, had resolved. Analysis of tested food or treat samples revealed a median thyroxine concentration for suspect products of 1.52 μg of thyroxine/g, whereas that of unrelated commercial foods was 0.38 μg of thyroxine/g. Results indicated that thyrotoxicosis can occur secondary to consumption of meat-based products presumably contaminated by thyroid tissue, and can be reversed by identification and elimination of suspect products from the diet.

Vitiligo and alopecia areata associated with subclinical/clinical hypothyroidism.

PubMed

Sehgal, Virendra N

2011-01-01

The parents of an 18-year-old woman had noticed white hair while combing their daughter's hair 12 years ago. They found tiny white spots on her scalp, but she was asymptomatic. The spots have since progressed. Examination of the affected skin on the scalp was marked by the presence of a chalky/ivory white macule, 8 to 10 cm in diameter, conforming to that of segmental (zosteriformis) vitiligo (Figure 1). The lesions were located on the temporoparietal region of the scalp. The hair over the macules was white (leukotrichia) and dry, coarse, and brittle. The patient's nails were thin and dull. Her thyroid profile revealed the following: triiodothyronine, 1.12 nmol/L (0.95-2.5 nmol/L); thyroxine, 69.21 nmol/L (60.0-120.0 nmol/L); and thyroid-stimulating hormone, 6.26 microIU/mL (0.25-5.00 microIU/mL), indicative of primary hypothyroidism. Liver and renal function tests were within normal limits. A lipid profile revealed the following: total lipids, 503.8 mg% (400-700 mg %); triglycerides, 123.0 mg % (160 mg %); cholesterol, 212.0 mg % (150-250 mg %); high-density lipoprotein, 43.1 mg % (30-63 mg %); and low-density lipoprotein, 144.3 mg % (50 mg %). Electrocardiographic findings were normal. History of tiredness, constipation, depression, sensitivity to cold, weight gain, muscle weakness, cramps, and increased menstrual flow supported the diagnosis. The patient was administered 100 microg of thyroxine once a day along with methoxsalen, the dose of which was calculated at 0.6 mg/kg to 0.7 mg/kg body weight per day given on alternate days, followed 2 hours later by exposure to UV-A (1 J/cm2) irradiation (psoralen-UV-A [PUVA]), supplemented by 1 mg of beta-methasone, 150 mg of levamisole on 2 consecutive days per week, and an antioxidant. During the course of 7 weeks, the macules (13 exposures) had become erythematous, with an appearance of perifollicular/ marginal pigmentation. Repeat examination showed a thyroid profile of total triiodothyronine (T3), 127.3 microg/dL (86-186); total thyroxine (T4), 6.54 microg/dL (4.5-12.5 microg/dL); and thyroid-stimulating hormone (TSH), 0.32 microIU/mL (0.3-5.6 microIU/mL), supplemented by antithyroid microsomal peroxidase antibodies (thyroid microsomal antibody and thyroid peroxidase), 21.9 IU/mL (1-40 IU/mL), and antithyroglobulin antibodies, 78.1 U/mL (1-100 U/mL). During the patient's treatment period, 4 other patients with clinical symptoms and signs of long-standing hypothyroidism developed vitiligo, the duration of which was variable in each patient (Table I). All of the patients were taking thyroxin. Thyroid and lipid profiles were performed periodically to evaluate the progress (Table I). These patients were also treated with PUVA therapy and thyroxin. During the course of treatment, 2 of the patients noticed asymptomatic, progressive, localized, and well-circumscribed hair loss at the temporal region of the scalp that extended to involve the vertex, conforming to findings of alopecia areata (Figure 2A and Figure 2B).

Congenital hypothyroidism from complete iodide transport defect: long-term evolution with iodide treatment.

PubMed Central

Albero, R.; Cerdan, A.; Sanchez Franco, F.

1987-01-01

Hypothyroidism from iodide transport deficiency is a rare disease, especially when found in two affected siblings. Treatment with high doses of iodide has been recommended, but no long term results have been reported. Two siblings with congenital hypothyroidism due to total failure to transport iodide have been followed up during twelve and a half years of treatment with oral potassium iodide. Iodine doses varied between 10.3 and 22 mg/day, and serum total iodine concentrations between 100 and 210 micrograms/dl. Total triiodothyronine (T3), thyroxine (T4) and free T4 were in the normal range during the time of study. Basal thyroid stimulating hormones (TSH) and maximum TSH response to thyrotrophin releasing hormone (TRH) were also in the range of normal values. These data along with clinical findings confirmed the potential usefulness of iodine in hypothyroidism due to complete iodide transport defect. PMID:3451231

Stimulation of neurotrophic factors and inhibition of proinflammatory cytokines by exogenous application of triiodothyronine in the rat model of ischemic stroke.

PubMed

Sabbaghziarani, Fatemeh; Mortezaee, Keywan; Akbari, Mohammad; Kashani, Iraj Ragerdi; Soleimani, Mansooreh; Hassanzadeh, Gholamreza; Zendedel, Adib

2017-01-01

There is a positive relation between decreases of triiodothyronine (T3) amounts and severity of stroke. The aim of this study was to evaluate the effect of exogenous T3 application on levels of neurogenesis markers in the subventricular zone. Cerebral ischemia was induced by middle cerebral artery occlusion in male Wistar rats. There were 4 experimental groups: sham, ischemic, vehicle, and treatment. Rats were injected with T3 (25 μg/kg, IV injection) at 24 hours after ischemia. Animals were sacrificed at day 7 after ischemia. There were high levels of brain-derived neurotrophic factor, nestin, and Sox2 expressions in gene and protein levels in the T3 treatment group (P ≤ .05 vs ischemic group). Treatment group showed high levels of sera T3 and thyroxine (T4) but low levels of thyrotropin (TSH), tumor necrosis factor-α, and interleukin-6 (P ≤ .05 vs ischemic group) at day 4 after ischemia induction. Findings of this study revealed the effectiveness of exogenous T3 application in the improvement of neurogenesis possibly via regulation of proinflammatory cytokines. Copyright © 2017 John Wiley & Sons, Ltd.

Estimation of iodine nutrition and thyroid function status in late-gestation pregnant women in the United States: Development and application of a population-based pregnancy model.

PubMed

Lumen, A; George, N I

2017-01-01

Previously, a deterministic biologically-based dose-response (BBDR) pregnancy model was developed to evaluate moderate thyroid axis disturbances with and without thyroid-active chemical exposure in a near-term pregnant woman and fetus. In the current study, the existing BBDR model was adapted to include a wider functional range of iodine nutrition, including more severe iodine deficiency conditions, and to incorporate empirically the effects of homeostatic mechanisms. The extended model was further developed into a population-based model and was constructed using a Monte Carlo-based probabilistic framework. In order to characterize total (T4) and free (fT4) thyroxine levels for a given iodine status at the population-level, the distribution of iodine intake for late-gestation pregnant women in the U.S was reconstructed using various reverse dosimetry methods and available biomonitoring data. The range of median (mean) iodine intake values resulting from three different methods of reverse dosimetry tested was 196.5-219.9μg of iodine/day (228.2-392.9μg of iodine/day). There was minimal variation in model-predicted maternal serum T4 and ft4 thyroxine levels from use of the three reconstructed distributions of iodine intake; the range of geometric mean for T4 and fT4, was 138-151.7nmol/L and 7.9-8.7pmol/L, respectively. The average value of the ratio of the 97.5th percentile to the 2.5th percentile equaled 3.1 and agreed well with similar estimates from recent observations in third-trimester pregnant women in the U.S. In addition, the reconstructed distributions of iodine intake allowed us to estimate nutrient inadequacy for late-gestation pregnant women in the U.S. via the probability approach. The prevalence of iodine inadequacy for third-trimester pregnant women in the U.S. was estimated to be between 21% and 44%. Taken together, the current work provides an improved tool for evaluating iodine nutritional status and the corresponding thyroid function status in pregnant women in the U.S. This model enables future assessments of the relevant risk of thyroid hormone level perturbations due to exposure to thyroid-active chemicals at the population-level. Published by Elsevier Inc.

Sobetirome and its Amide Prodrug Sob-AM2 Exert Thyromimetic Actions in Mct8-Deficient Brain.

PubMed

Bárez-López, Soledad; Hartley, Meredith D; Grijota-Martínez, Carmen; Scanlan, Thomas S; Guadaño-Ferraz, Ana

2018-06-29

Loss of function mutations in the thyroid hormone (TH)-specific cell membrane transporter, the monocarboxylate transporter 8 (MCT8), lead to profound psychomotor retardation and abnormal TH serum levels, with low thyroxine (T4) and high triiodothyronine (T3). Several studies point to impaired TH transport across brain barriers as a crucial pathophysiological mechanism resulting in cerebral hypothyroidism. Treatment options for MCT8-deficient patients are limited and are focused on overcoming the brain barriers. The aim of this study was to evaluate the ability of the TH analog sobetirome and its prodrug Sob-AM2 to access the brain and exert thyromimetic actions in the absence of Mct8. Juvenile wild-type (Wt) mice and mice lacking Mct8 and deiodinase type 2 (Mct8/Dio2KO) were treated systemically with daily injections of vehicle, 1 mg of sobetirome/kg body weight/day, or 0.3 mg of Sob-AM2/kg body weight/day for seven days. Sobetirome content was measured using liquid chromatography-tandem mass spectrometry, and T4 and T3 levels by specific radioimmunoassays. The effect of sobetirome treatment in the expression of T3-dependent genes was measured in the heart, liver, and cerebral cortex by real-time polymerase chain reaction. Sob-AM2 treatment in Mct8/Dio2KO animals led to 1.8-fold more sobetirome content in the brain and 2.5-fold less in plasma in comparison to the treatment with the parent drug sobetirome. Both sobetirome and Sob-AM2 treatments in Mct8/Dio2KO mice greatly decreased plasma T4 and T3 levels. Dio1 and Ucp2 gene expression was altered in the liver of Mct8/Dio2KO mice and was not affected by the treatments. In the heart, Hcn2 but not Atp2a2 expression was increased after treatment with the analogs. Interestingly, both sobetirome and Sob-AM2 treatments increased the expression of several T3-dependent genes in the brain such as Hr, Abcd2, Mme, and Flywch2 in Mct8/Dio2KO mice. Sobetirome and its amide prodrug Sob-AM2 can access the brain in the absence of Mct8 and exert thyromimetic actions modulating the expression of T3-dependent genes. At the peripheral level, the administration of these TH analogs results in the depletion of circulating T4 and T3. Therefore, sobetirome and Sob-AM2 have the potential to address the cerebral hypothyroidism and the peripheral hyperthyroidism characteristic of MCT8 deficiency.

Production rates and turnover of triiodothyronine in rat-developing cerebral cortex and cerebellum. Responses to hypothyroidism

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

Silva, J.E.; Matthews, P.S.

1984-09-01

Local 5'-deiodination of serum thyroxine (T4) is the main source of triiodothyronine (T3) for the brain. Since we noted in previous studies that the cerebral cortex of neonatal rats tolerated marked reductions in serum T4 without biochemical hypothyroidism, we examined the in vivo T4 and T3 metabolism in that tissue and in the cerebellum of euthyroid and hypothyroid 2-wk-old rats. We also assessed the contribution of enhanced tissue T4 to T3 conversion and decreased T3 removal from the tissues to the T3 homeostasis in hypothyroid brain. Congenital and neonatal hypothyroidism was induced by adding methimazole to the drinking water. Serum,more » cerebral cortex (Cx), cerebellum (Cm), liver (L) and kidney (R) concentrations of 125I-T4, 125I-T3(T4), and 131I-T3 were measured at various times after injecting 125I-T4 and 131I-T3. The rate of T3 removal from the tissues was measured after injecting an excess of anti-T3-antibody to rats previously injected with tracer T3. In hypothyroidism, the fractional removal rates and clearances were reduced in all tissues, in cortex and cerebellum by 70%, and in liver and kidney ranging from 30 to 50%. While greater than 80% of the 125I-T3(T4) in the brain tissues of euthyroid rats was locally produced, in hypothyroid cerebral cortex and cerebellum the integrated concentrations of 125I-T3(T4) were 2.7- and 1.5-fold greater than in euthyroid rats.« less

Effects of chronic exposure to triclosan on reproductive and thyroid endpoints in the adult Wistar female rat.

PubMed

Louis, Gwendolyn W; Hallinger, Daniel R; Braxton, M Janay; Kamel, Alaa; Stoker, Tammy E

2017-01-01

Triclosan (TCS), an antibacterial, has been shown to be an endocrine disruptor in the rat. Previously, subchronic TCS treatment to female rats was found to advance puberty and potentiate the effect of ethinyl estradiol (EE) on uterine growth when EE and TCS were co-administered prior to weaning. In the pubertal study, a decrease in serum thyroxine (T 4 ) concentrations with no significant change in serum thyroid-stimulating hormone (TSH) was also observed. The purpose of the present study was to further characterize the influence of TCS on the reproductive and thyroid axes of the female rat using a chronic exposure regimen. Female Wistar rats were exposed by oral gavage to vehicle control, EE (1 μg/kg), or TCS (2.35, 4.69, 9.375 or 37.5 mg/kg) for 8 months and estrous cyclicity monitored. Although a divergent pattern of reproductive senescence appeared to emerge from 5 to 11 months of age between controls and EE-treated females, no significant difference in cyclicity was noted between TCS-treated and control females. A higher % control females displayed persistent diestrus (PD) by the end of the study, whereas animals administered with positive control (EE) were predominately persistent estrus (PE). Thyroxine concentration was significantly decreased in TCS-administered 9.375 and 37.5 mg/kg groups, with no marked effects on TSH levels, thyroid tissue weight, or histology. Results demonstrate that a long-term exposure to TCS did not significantly alter estrous cyclicity or timing of reproductive senescence in females but suppressed T 4 levels at a lower dose than previously observed.

Clinical evaluation of a novel liquid formulation of L-thyroxine for once daily treatment of dogs with hypothyroidism.

PubMed

Le Traon, G; Brennan, S F; Burgaud, S; Daminet, S; Gommeren, K; Horspool, L J I; Rosenberg, D; Mooney, C T

2009-01-01

A liquid solution of levothyroxine (L-T4) is available for treatment of canine hypothyroidism. Once daily oral administration of a liquid L-T4 solution is effective and safe for controlling hypothyroidism in dogs. Thirty-five dogs with naturally occurring hypothyroidism. Dogs received L-T4 solution PO once daily at a starting dosage of 20 microg/kg body weight (BW). The dose was adjusted every 4 weeks, based on clinical signs and peak serum total T4 (tT4) concentrations. Target peak serum tT4 and thyroid stimulating hormone (TSH) concentrations, 4-6 hours posttreatment, were 35-95 nmol/L and < 0.68 ng/mL, respectively. Dogs were followed for up to 22 weeks after establishment of the maintenance dose. Clinical signs of hypothyroidism improved or resolved in 91% of dogs after 4 weeks of L-T4 treatment at 20 microg/kg once daily. The maintenance dose was established in 76, 94, and 100% of dogs after 4, 8, and 12 weeks of treatment, respectively. This was 20 microg L-T4/kg BW for 79% of the dogs, 30 microg/kg BW for 15%, and 10-15 microg/kg BW in the remaining 6%, once daily. Thereafter, median peak tT4 and TSH concentrations were 51 nmol/L and 0.18 ng/mL, respectively, and remained stable during the 22-week follow-up; clinical signs did not recur. All of the hypothyroid dogs had rapid clinical and hormonal responses to supplementation with the PO-administered L-T4 solution. The starting dosage of 20 microg L-T4/kg BW once daily was suitable for 79% of dogs.

Effect of thyroxine on munc-18 and syntaxin-1 expression in dorsal hippocampus of adult-onset hypothyroid rats

PubMed Central

Zhu, Y.; Ning, D.; Wang, F.; Liu, C.; Xu, Y.; Jia, X.; Zhu, D.

2012-01-01

Adult-onset hypothyroidism induces a variety of impairments on hippocampus- dependent neurocognitive functioningin which many synaptic proteins in hippocampus neurons are involved. Here, we observed the effect of adult-onset hypothyroidism on the expression of syntaxin-1 and munc-18 in the dorsal hippocampus and whether the altered proteins could be restored by levothyroxine (T4) treatment. All rats were separated into 4 groups randomly: hypothyroid group, 5 µg T4 /100 g body weight (BW) treated group, 20 µg T4/100 g BW treated group and control group. The radioimmunoassay kits were applied to assay the levels of serum T3 and T4, and the levels of syntaxin-1 and munc-18 in hippocampus were assessed by immunohistochemistry and Western blot. Both analysis corroborated that syntaxin-1 in the hypothyroid group was significantly higher. Munc-18 was lower in four layers of CA3 and dentate gyrus by immunohistochemistry. After two weeks of treatment with 5 µg T4/100 g BW for hypothyroidism, syntaxin-1 levels were completely restored, whereas the recovery of munc-18 only located in two of the four impaired layers. Twenty µg T4/100 g BW treatment normalized munc-18 levels. These data suggested that adult-onset hypothyroidism induced increment of syntaxin-1 and decrement of munc-18 in the dorsal hippocampus, which could be restored by T4 treatment. Larger dosage of T4 caused more effective restorations. PMID:22688303

Different adaptations of Chinese winter-over expeditioners during prolonged Antarctic and sub-Antarctic residence.

PubMed

Chen, Nan; Wu, Quan; Li, Hao; Zhang, Tao; Xu, Chengli

2016-05-01

Prolonged residence in Antarctica is characterized by exposure to isolated, confined, and extreme (ICE) environment. Winter-over expeditioners at research stations often exhibit a complex of psychophysiological symptoms, which varied by stations and sociocultural backgrounds. To understand the different patterns of psychophysiological responses provoked by environmental stress, we conducted a longitudinal assessment of mood and endocrine function in two groups of Chinese expeditioners who were deployed to sub-Antarctic (Great Wall Station, 62°S, N = 12) and Antarctic (Zhongshan Station, 66°S, N = 16) from December 2003 to 2005. Measures of mood, thyroid function, the levels of plasma catecholamine, and circulating interleukins were obtained at departure from China, mid-winter (Antarctica), end of winter (Antarctica), and return to China, respectively. The Zhongshan Station crew experienced significant increases in fatigue, anger, tension, confusion, and decrease in free thyroxine (FT4), norepinephrine (NE), and epinephrine (E) during the winter, increase in thyrotropin (TSH) and total triiodothyronine (TT3) when returning, whereas their counterparts at Great Wall Station only experienced increased TT3 after deployment. Moreover, compared with the Great Wall Station crew, the Zhongshan Station crew exhibited greater increase in anger, greater decrease in FT4, total thyroxine (TT4), NE and E over the winter, and greater increase in TSH when returning. Chinese expeditioners who lived and worked at the Antarctic station and the sub-Antarctic station for over a year showed different change patterns in mood and endocrine hormones. Negative mood and endocrine dysfunction were positively associated with the severity of environment. The study is a supplement to scientific knowledge on psychophysiological variation under ICE environment, which has certain applied value for the development of preventive countermeasures or interventions.

Different adaptations of Chinese winter-over expeditioners during prolonged Antarctic and sub-Antarctic residence

NASA Astrophysics Data System (ADS)

Chen, Nan; Wu, Quan; Li, Hao; Zhang, Tao; Xu, Chengli

2016-05-01

Prolonged residence in Antarctica is characterized by exposure to isolated, confined, and extreme (ICE) environment. Winter-over expeditioners at research stations often exhibit a complex of psychophysiological symptoms, which varied by stations and sociocultural backgrounds. To understand the different patterns of psychophysiological responses provoked by environmental stress, we conducted a longitudinal assessment of mood and endocrine function in two groups of Chinese expeditioners who were deployed to sub-Antarctic (Great Wall Station, 62°S, N = 12) and Antarctic (Zhongshan Station, 66°S, N = 16) from December 2003 to 2005. Measures of mood, thyroid function, the levels of plasma catecholamine, and circulating interleukins were obtained at departure from China, mid-winter (Antarctica), end of winter (Antarctica), and return to China, respectively. The Zhongshan Station crew experienced significant increases in fatigue, anger, tension, confusion, and decrease in free thyroxine (FT4), norepinephrine (NE), and epinephrine (E) during the winter, increase in thyrotropin (TSH) and total triiodothyronine (TT3) when returning, whereas their counterparts at Great Wall Station only experienced increased TT3 after deployment. Moreover, compared with the Great Wall Station crew, the Zhongshan Station crew exhibited greater increase in anger, greater decrease in FT4, total thyroxine (TT4), NE and E over the winter, and greater increase in TSH when returning. Chinese expeditioners who lived and worked at the Antarctic station and the sub-Antarctic station for over a year showed different change patterns in mood and endocrine hormones. Negative mood and endocrine dysfunction were positively associated with the severity of environment. The study is a supplement to scientific knowledge on psychophysiological variation under ICE environment, which has certain applied value for the development of preventive countermeasures or interventions.

Skin-resident memory CD4+ T cells enhance protection against Leishmania major infection.

PubMed

Glennie, Nelson D; Yeramilli, Venkata A; Beiting, Daniel P; Volk, Susan W; Weaver, Casey T; Scott, Phillip

2015-08-24

Leishmaniasis causes a significant disease burden worldwide. Although Leishmania-infected patients become refractory to reinfection after disease resolution, effective immune protection has not yet been achieved by human vaccines. Although circulating Leishmania-specific T cells are known to play a critical role in immunity, the role of memory T cells present in peripheral tissues has not been explored. Here, we identify a population of skin-resident Leishmania-specific memory CD4+ T cells. These cells produce IFN-γ and remain resident in the skin when transplanted by skin graft onto naive mice. They function to recruit circulating T cells to the skin in a CXCR3-dependent manner, resulting in better control of the parasites. Our findings are the first to demonstrate that CD4+ TRM cells form in response to a parasitic infection, and indicate that optimal protective immunity to Leishmania, and thus the success of a vaccine, may depend on generating both circulating and skin-resident memory T cells. © 2015 Glennie et al.

Skin-resident memory CD4+ T cells enhance protection against Leishmania major infection

PubMed Central

Glennie, Nelson D.; Yeramilli, Venkata A.; Beiting, Daniel P.; Volk, Susan W.; Weaver, Casey T.

2015-01-01

Leishmaniasis causes a significant disease burden worldwide. Although Leishmania-infected patients become refractory to reinfection after disease resolution, effective immune protection has not yet been achieved by human vaccines. Although circulating Leishmania-specific T cells are known to play a critical role in immunity, the role of memory T cells present in peripheral tissues has not been explored. Here, we identify a population of skin-resident Leishmania-specific memory CD4+ T cells. These cells produce IFN-γ and remain resident in the skin when transplanted by skin graft onto naive mice. They function to recruit circulating T cells to the skin in a CXCR3-dependent manner, resulting in better control of the parasites. Our findings are the first to demonstrate that CD4+ TRM cells form in response to a parasitic infection, and indicate that optimal protective immunity to Leishmania, and thus the success of a vaccine, may depend on generating both circulating and skin-resident memory T cells. PMID:26216123

Thyroid-Stimulating Hormone Suppression for Protection Against Hypothyroidism Due to Craniospinal Irradiation for Childhood Medulloblastoma/Primitive Neuroectodermal Tumor

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

Massimino, Maura; Gandola, Lorenza; Collini, Paola

Purpose: Hypothyroidism is one of the earliest endocrine effects of craniospinal irradiation (CSI). The effects of radiation also depend on circulating thyroid-stimulating hormone (TSH), which acts as an indicator of thyrocyte function and is the most sensitive marker of thyroid damage. Hence, our study was launched in 1998 to evaluate the protective effect of TSH suppression during CSI for medulloblastoma/primitive neuroectodermal tumor. Patients and Methods: From Jan 1998 to Feb 2001, a total of 37 euthyroid children scheduled for CSI for medulloblastoma/primitive neuroectodermal tumor underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginningmore » and end of CSI. From 14 days before and up to the end of CSI, patients were administered L-thyroxine at suppressive doses; every 3 days, TSH suppression was checked to ensure a value <0.3 {mu}M/ml. During follow-up, blood tests and ultrasound were repeated after 1 year; primary hypothyroidism was considered an increased TSH level greater than normal range. CSI was done using a hyperfractionated accelerated technique with total doses ranging from 20.8-39 Gy; models were used to evaluate doses received by the thyroid bed. Results: Of 37 patients, 25 were alive a median 7 years after CSI. They were well matched for all clinical features, except that eight children underwent adequate TSH suppression during CSI, whereas 17 did not. Hypothyroidism-free survival rates were 70% for the 'adequately TSH-suppressed' group and 20% for the 'inadequately TSH-suppressed' group (p = 0.02). Conclusions: Thyroid-stimulating hormone suppression with L-thyroxine had a protective effect on thyroid function at long-term follow-up. This is the first demonstration that transient endocrine suppression of thyroid activity may protect against radiation-induced functional damage.« less

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).

Immune stimulation improves endocrine and neural fetal outcomes in a model of maternofetal thyrotoxicosis.

PubMed

Ahmed, R G; Abdel-Latif, M; Mahdi, Emad A; El-Nesr, Khalid A

2015-12-01

The potentiation of the immune system in pregnant rats was performed with Complete Freund's Adjuvant [CFA; 20μl, subcutaneous at gestation day (GD) 18] in experimentally-induced hyperthyroidism by Levo-thyroxine (L-T4; 10μg/100g of b.w., intraperitoneal from GD 2 to 17). The potential effects on the fetal neuroendocrine function were evaluated by observing some histopathological investigations in pregnant rats and measuring some biochemical parameters in dams and their fetuses at GD 20. In hyperthyroid group, an increase in maternofetal serum thyroxine (T4), triiodothyronine (T3) and a decrease in thyrotropin (TSH) levels were noticed, while the concentrations of fetal serum growth hormone (GH) and insulin-like growth factor-1 (IGF1) levels were increased at tested GD with respect to control and CFA groups. Moreover, the activity of uterine and placental myeloperoxidase (MPO) was increased (P<0.001) in CFA and CFA-treated hyperthyroid groups in respect to control or hyperthyroid groups, respectively. The gestational thyrotoxicosis led to some histopathological lesions in uterine and placental tissues characterized by severe degeneration in trophoblast spongioblast cell layer with congestion, mild congested blood vessels in the endometrium and deficient in spiral artery remodeling. Although, the elevation in fetal serum transforming growth factor-beta (TGFβ) and cerebellar monoamines [norepineprine (NE), epinephrine (E), dopamine (DA) and 5-hydroxytryptamine (5-HT)] was observed, the reduction in fetal serum tumor necrosis factor-alpha (TNFα) and adipokines (Leptin and adiponectin) was detected. Treatment of dams with CFA showed an obviously reversing and protecting effect against hyperthyroid perturbations. Thus, the maternal CFA can be used in treatment of the fetal neuroendocrine dysfunctions. Copyright © 2015 Elsevier B.V. All rights reserved.

Dietary Management of Hyperthyroidism in a Dog.

PubMed

Looney, Andrea; Wakshlag, Joseph

An 8 yr old female spayed golden retriever presented for a routine exam during which ventral cervical soft tissue masses were identified. History included weight loss, increased activity and appetite, gagging, and occasional diarrhea. Exam findings included a body condition score of 4/9 and palpable ventral cervical nodules. A serum thyroxine (T4) value was 8.0 ug/dL (normal = 0.8-3.5ug/dL). Doppler systolic blood pressure readings ranged from 200-210 mmHg (normal systolic blood pressure <150 mmHg). The diagnosis was hyperthyroidism due to active thyroid masses. Due to financial constraints, the owner elected conservative management. Initial treatment with methimazole resulted in a decreased T4 value of 5.0 ug/dL at approximately 4 mo after initiation of treatment. A commercially available iodine-restricted feline diet was fed and this resulted in further reduction in serum T4 levels, improved sleeping cycles, reduced anxiety, and reduced systolic blood pressure. A temporary suspension of iodine-restricted feline diet for 2 mo resulted in increases in serum T4 concentrations, which, subsequently, decreased with re-introduction of the diet. Roughly 10 mo after initiation of the therapeutic diet and 16 mo after intial diagnosis, the dog remains relatively normal clinically despite active growing cervical masses with T4 concentration of 2.3 ug/dL.

Association Between Serum Levels of Adipocyte Fatty Acid-binding Protein and Free Thyroxine

PubMed Central

Tseng, Fen-Yu; Chen, Pei-Lung; Chen, Yen-Ting; Chi, Yu-Chao; Shih, Shyang-Ron; Wang, Chih-Yuan; Chen, Chi-Ling; Yang, Wei-Shiung

2015-01-01

Abstract Adipocyte fatty acid-binding protein (AFABP) has been shown to be a biomarker of body weight change and atherosclerosis. Changes in thyroid function are associated with changes in body weight and risks of cardiovascular diseases. The association between AFABP and thyroid function status has been seldom evaluated. The aim of this study was to compare the serum AFABP concentrations in hyperthyroid patients and those in euthyroid individuals, and to evaluate the associations between serum AFABP and free thyroxine (fT4) levels. For this study, 30 hyperthyroid patients and 30 euthyroid individuals at a referral medical center were recruited. The patients with hyperthyroidism were treated with antithyroid regimens as clinically indicated. No medication was given to the euthyroid individuals. The body weight, body mass index, thyroid function, serum levels of AFABP, and biochemical data of both groups at baseline and at the 6th month were compared. Associations between AFABP and fT4 levels were also analyzed. At the baseline, the hyperthyroid patients had significantly higher serum AFABP levels than the euthyroid individuals (median [Q1, Q3]: 22.8 [19.4, 30.6] ng/mL vs 18.6 [15.3, 23.2] ng/mL; P = 0.038). With the antithyroid regimens, the AFABP serum levels of the hyperthyroid patients decreased to 16.6 (15.0, 23.9) ng/mL at the 6th month. No difference in the AFABP level was found between the hyperthyroid and the euthyroid groups at the 6th month. At baseline, sex (female vs male, ß = 7.65, P = 0.022) and fT4 level (ß = 2.51, P = 0.018) were significantly associated with AFABP levels in the univariate regression analysis. At the 6th month, sex and fT4 level (ß = 8.09, P < 0.001 and ß = 3.61, P = 0.005, respectively) were also significantly associated with AFABP levels. The associations between sex and fT4 level with AFABP levels remained significant in the stepwise multivariate regression analysis, both at baseline and at the 6th month. The patients with hyperthyroidism had higher serum AFABP levels than the individuals with euthyroidism. In the patients with hyperthyroidism, the serum AFABP concentrations decreased after the antithyroid treatment. In this study, the serum AFABP concentrations were positively associated with female sex and the serum fT4 level. PMID:26469926

IL-6-driven STAT signalling in circulating CD4+ lymphocytes is a marker for early anticitrullinated peptide antibody-negative rheumatoid arthritis.

PubMed

Anderson, Amy E; Pratt, Arthur G; Sedhom, Mamdouh A K; Doran, John Paul; Routledge, Christine; Hargreaves, Ben; Brown, Philip M; Lê Cao, Kim-Anh; Isaacs, John D; Thomas, Ranjeny

2016-02-01

A previously identified signal transduction and activator of transcription-3 (STAT3) target-enriched gene signature in circulating CD4+ T cells of patients with early rheumatoid arthritis (RA) was prominent in autoantibody-negative individuals. Here, interleukin (IL)-6-mediated STAT signalling was investigated in circulating lymphocytes of an independent early arthritis patient cohort, seeking further insight into RA pathogenesis and biomarkers of potential clinical utility. Constitutive and IL-6-induced expression of phosphorylated STAT1 (pSTAT1) and pSTAT3 was determined in T and B cells using Phosflow cytometric analysis in patients with RA and controls. Contemporaneous levels of serum cytokines were measured by immunoassay. Induced gene expression was measured in cultured CD4+T cells by quantitative real-time PCR. Among circulating lymphocytes of 187 patients with early arthritis, constitutive pSTAT3 correlated with serum IL-6 levels maximally in CD4+ T cells. Increased constitutive pSTAT3, but not pSTAT1, was observed in circulating CD4+ T cells of patients with early anticitrullinated peptide autoantibody (ACPA)-negative RA compared with disease controls, and these levels decreased alongside markers of disease activity with IL-6R-targeted treatment. Among patients presenting with seronegative undifferentiated arthritis (UA) the ratio of constitutive pSTAT3:pSTAT1 in CD4+ T cells contributed substantially to an algorithm for predicting progression to classifiable RA during a median of 20 months follow-up (area under receiver operator characteristic curve=0.84; p<0.001). Our findings support a particular role for IL-6-driven CD4+ T cell activation via STAT3 during the induction of RA, particularly as a feature of ACPA-negative disease. CD4+ T cell pSTAT measurements show promise as biomarkers of UA-RA progression and now require independent validation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

Kuni, C.C.; Klingensmith, W.C. III

Thirteen patients received an initial dose of 25-29.9 mCi (925-1106 MBq) of /sup 131/I following partial thyroidectomy for papillary, follicular, or mixed carcinoma. Administration of thyroxine (T/sub 4/) or triiodothyronine (T/sub 3/) was stopped 3-12 weeks and 1-6 weeks, respectively, before therapy or imaging. Patients remained on normal diets and did not receive thyroid stimulating hormone (TSH) or diuretics. Follow-up 3 months to 2 years after therapy demonstrated that ablation of thyroid bed activity was successful in only one patient, who still had metastases. This suggests that administration of 25-29.9 mCi of /sup 131/I following surgery is unreliable for ablationmore » of residual thyroid bed activity.« less

Serum cortisol and thyroxine concentrations as predictors of death in critically ill puppies with parvoviral diarrhea.

PubMed

Schoeman, Johan P; Goddard, Amelia; Herrtage, Michael E

2007-11-15

To evaluate the role of adrenal and thyroid hormones in the prediction of death in a population of critically ill puppies with parvoviral diarrhea by measuring serial daily serum concentrations of cortisol and thyroxine. Prospective case-control study. 57 critically ill puppies with parvoviral diarrhea admitted to the hospital and 17 clinically normal control puppies. Basal serum cortisol and thyroxine concentrations were measured for each dog with parvoviral diarrhea at admission (prior to treatment) and daily until death, euthanasia, or discharge. Median time between admission and death was 48 hours (ie, on day 3). Median serum cortisol concentration on day 1 (admission) in all dogs with parvoviral diarrhea (248 nmol/L) was significantly higher than in control dogs (77 nmol/L). No significant difference was found in the day 1 median serum cortisol concentration of 11 dogs that died (302 nmol/L) and 46 dogs that survived (238 nmol/L). A significantly higher median serum cortisol concentration was, however, found in nonsurvivor group dogs, compared with survivor group dogs, on days 2 and 3. Median serum thyroxine concentration on day 1 in dogs with parvoviral diarrhea was significantly lower than in control dogs (8.12 nmol/L vs 35 nmol/L, respectively). Median serum thyroxine concentration of nonsurvivor group dogs (4.4 nmol/L) was significantly lower than that of survivor group dogs (9.2 nmol/L) at admission and became even lower on days 2 and 3. High serum cortisol and low serum thyroxine concentrations at 24 and 48 hours after admission were associated with death in dogs with parvoviral diarrhea.

Thyroid gland function during cross adaptation to heat and cold in man

NASA Astrophysics Data System (ADS)

Sridharan, K.; Sawhney, R. C.; Mathew, L.; Pichan, G.; Malhotra, A. S.

1986-09-01

Plasma thyroxine (T4), triiodothyronine (T3) and thyrotropin (TSH) levels were monitored in 10 healthy euthyroid male subjects of the age group 20 to 30 years before and during heat and cold acclimatisation schedule in a sequential manner. The subjects were exposed to 45‡C DB and 30% relative humidity in a hot chamber for 2 hours daily for 8 consecutive days. Subsequently they were exposed to cold for 4 hours daily at 10‡C for 21 days. The mean plasma T4 and T3 concentration before exposure to heat were 7.87±0.82 ug/dl and 159.8±9.1 ng/dl respectively. A significant decrease in both T4 (p<0.05) and T3 (p<0.01) levels to mean values of 6.4±0.76 Μg/dl and 129±7.9 ng/dl was recorded on day 4 of exposure to heat. Further significant decrease (p<0.05) over the preceding T3 levels was observed on day 8 of heat exposure. Plasma T4 and T3 on day 21 of cold exposure was not significantly different from the levels reckoned after last day of heat exposure but was significantly lower than the pre-exposure values. Throughout the thermal stress schedule there was no change in the TSH levels. These observations suggest that a decrease in thyroid hormone levels during exposure to heat might be an adaptive process which continues even during cold acclimatisation.

Thyroid hormones and thermogenesis: the metabolic cost of food and exercise.

PubMed

Acheson, K; Jéquier, E; Burger, A; Danforth, E

1984-03-01

To mimic plasma T3 levels observed in a previous overfeeding study, six lean healthy men received replacement amounts of L-thyroxine (200 micrograms/d) to block endogenous thyroid hormone production while consuming their habitual diet. After 4 weeks equilibration on T4, L-triiodothyronine (T3) was given (45 micrograms/d) in addition to T4, to produce mild T3-thyrotoxicosis, for another 2 weeks. At the end of this period T3 was discontinued but the subjects continued to receive T4 for another 2 weeks. Resting metabolic rate, exercise efficiency, and the thermic effect of food were measured using a ventilated hood, open circuit indirect calorimeter at the end of each phase of the experiment. There was a significant increase in the resting metabolic rate of 6% (P less than 0.01) while the subjects were mildly T3-thyrotoxic. The increase in energy expenditure however, during exercise on a bicycle ergometer or following a 500 kcal liquid-formula meal remained unaltered in the same situation. Thus, mild T3-toxicosis does not alter the efficiency of exercise or the thermic effect of food. These results suggest that the increased plasma T3 levels, observed in overfeeding, could explain corresponding increases in resting metabolic rate but not changes in the efficiency of exercise or the utilization of food.

Effects of oral administration of levothyroxine sodium on serum concentrations of thyroid gland hormones and responses to injections of thyrotropin-releasing hormone in healthy adult mares.

PubMed

Sommardahl, Carla S; Frank, Nicholas; Elliott, Sarah B; Webb, Latisha L; Refsal, Kent R; Denhart, Joseph W; Thompson, Donald L

2005-06-01

To determine the effects of levothyroxine sodium (L-T4) on serum concentrations of thyroid gland hormones and responses to injections of thyrotropin-releasing hormone (TRH) in euthyroid horses. 12 healthy adult mares. 8 horses received an incrementally increasing dosage of L-T4 (24, 48, 72, or 96 mg of L-T4/d) for weeks 1 to 8. Each dose was provided for 2 weeks. Four additional horses remained untreated. Serum concentrations of total triiodothyronine (tT3), total thyroxine (tT4), free T3 (fT3), free T4 (fT4), and thyroid-stimulating hormone (TSH) were measured in samples obtained at weeks 0, 2, 4, 6, and 8; 1.2 mg of TRH was then administered i.v., and serum concentrations of thyroid gland hormones were measured 2 and 4 hours after injection. Serum reverseT3 (rT3) concentration was also measured in the samples collected at weeks 0 and 8. Treated horses lost a significant amount of weight (median, 19 kg). Significant treatment-by-time effects were detected for serum tT3, tT4, fT3, fT4, and TSH concentrations, and serum tT4 concentrations were positively correlated (r, 0.95) with time (and therefore dosage) in treated horses. Mean +/- SD serum rT3 concentration significantly increased in treated horses (3.06 +/- 0.51 nmol/L for week 8 vs 0.74 +/- 0.22 nmol/L for week 0). Serum tT3, tT4, fT3, and TSH concentrations in response to TRH injections differed significantly between treated and untreated horses. Administration of levothyroxine sodium increased serum tT4 concentrations and blunted responses toTRH injection in healthy euthyroid horses.

Changes in vascular reactivity induced by acute hyperthyroidism in isolated rat aortae.

PubMed

Honda, H; Iwata, T; Mochizuki, T; Kogo, H

2000-06-01

Hyperthyroidism was induced by subcutaneous injections of L-thyroxine (T(4)) (500 mg/kg/day) for 3 days in order to study whether adrenergic and muscarinic receptor-mediated vascular responses alter at an early stage of the disease. T(4) treatment was sufficient to induce a significant degree of thyroid weight loss, tachycardia, cardiac hypertrophy, and an elevation in serum T(4) levels. The tension of aortic ring preparations isolated from rats was measured isometrically to investigate the influence of acute hyperthyroidism. The contractions induced by norepinephrine (NE) were significantly suppressed in aortic rings from rats treated with T(4) compared with control rats. N(G)-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide synthase (NOS), significantly enhanced NE-induced contraction in aortic rings from both control and T(4)-treated rats, and the enhancement was greater in rats treated with T(4) than control rats. The relaxations induced by either acetylcholine (ACh) or sodium nitroprusside (SNP) were also significantly enhanced by T(4) treatment. L-NOARG abolished the relaxation induced by ACh in aortic rings from both control and T(4)-treated rats. L-NOARG shifted SNP-induced relaxation curves of aortic rings from those of control rats to the left, but not with rats treated with T(4). T(4) treatment showed no influence on the amount of endothelial NOS (eNOS) protein. These results suggest that vascular responses alter at an early stage of hyperthyroidism and that it may be due to a modification in the NO system which is independent from the amount of eNOS protein.

Assessment of levothyroxine sodium bioavailability: recommendations for an improved methodology based on the pooled analysis of eight identically designed trials with 396 drug exposures.

PubMed

Walter-Sack, Ingeborg; Clanget, Christof; Ding, Reinhard; Goeggelmann, Christoph; Hinke, Vera; Lang, Matthias; Pfeilschifter, Johannes; Tayrouz, Yorki; Wegscheider, Karl

2004-01-01

Assessment of dosage form performance in delivering endogenous compounds, such as hormones, in vivo requires a specific approach. Assessment of relative bioavailability of levothyroxine sodium (L-T4) from eight solid preparations, compared with a liquid formulation, by using pharmacological doses, and critical evaluation of trial methodology based on the pooled analysis of individual data. Eight open-label, randomised, single-dose, crossover phase I studies using eight solid L-T4 dosage forms (25, 50, 75, 100, 125, 150, 175, 200 microg per tablet; administered total doses 600, 625 or 700 microg) and a liquid formulation; assessment of relative bioavailability by 90% confidence intervals for the relative area under the concentration-time curve (AUC) of total thyroxine (TT4), i.e. protein-bound plus free thyroxine, calculated by using the recommended log AUC four-way analysis of variance models for crossover designs. For the pooled analysis, general linear models were applied to assess the validity of model assumptions, to identify potential sources of effect modification, to discuss alternative modelling approaches with respect to endogenous hormone secretion and to give recommendations for future designs and sample sizes. One hundred and sixty-nine healthy males; 29 of these individuals participating in two studies. Single oral doses of L-T4 tablets and the liquid formulation administered after fasting, separated by at least 6 weeks; a total of 396 drug exposures. TT4 AUC from 0 to 48 hours and peak plasma concentration with and without baseline correction. Each study demonstrated equivalence of the tablets to the drinking solution, independent of the chosen analysis model. Sequence effects that could devalidate the chosen crossover approach were not found. Period effects with changing directions that could best be explained by seasonal variation were detected. While the pre-specified method of baseline correction of simply subtracting individual time-zero TT4 values was disadvantageous, the analysis of total AUC could be improved considerably by covariate adjustment for baseline TT4. With this approach, sample sizes could have been substantially reduced or, alternatively, the recommended equivalence ranges could be reduced to +/-6%. Using a single pharmacological dose of L-T4 in two-period crossover designs is a safe and reliable procedure to assess L-T4 dosage form performance. With an adequate statistical modelling approach, the design is efficient and allows general conclusions with moderate sample sizes.

Development of the Larval Amphibian Growth and Development Assay: effects of chronic 4-tert-octylphenol or 17β-trenbolone exposure in Xenopus laevis from embryo to juvenile.

PubMed

Haselman, Jonathan T; Kosian, Patricia A; Korte, Joseph J; Olmstead, Allen W; Iguchi, Taisen; Johnson, Rodney D; Degitz, Sigmund J

2016-12-01

The Larval Amphibian Growth and Development Assay (LAGDA) is a globally harmonized test guideline developed by the U.S. Environmental Protection Agency in collaboration with Japan's Ministry of the Environment. The LAGDA was designed to evaluate apical effects of chronic chemical exposure on growth, thyroid-mediated amphibian metamorphosis and reproductive development. During the validation phase, two well-characterized endocrine-disrupting chemicals were tested to evaluate the performance of the initial assay design: xenoestrogen 4-tert-octylphenol (tOP) and xenoandrogen 17β-trenbolone (TB). Xenopus laevis embryos were exposed, in flow-through conditions, to tOP (nominal concentrations: 0.0, 6.25, 12.5, 25 and 50 µg l -1 ) or TB (nominal concentrations: 0.0, 12.5, 25, 50 and 100 ng l -1 ) until 8 weeks post-metamorphosis, at which time growth measurements were taken, and histopathology assessments were made of the gonads, reproductive ducts, liver and kidneys. There were no effects on growth in either study and no signs of overt toxicity, sex reversal or gonad dysgenesis. Exposure to tOP caused a treatment-related decrease in circulating thyroxine and an increase in thyroid follicular cell hypertrophy and hyperplasia (25 and 50 µg l -1 ) during metamorphosis. Müllerian duct development was affected after exposure to both chemicals; tOP exposure caused dose-dependent maturation of oviducts in both male and female frogs, whereas TB exposure caused accelerated Müllerian duct regression in males and complete regression in >50% of the females in the 100 ng l -1 treatment. Based on these results, the LAGDA performed adequately to evaluate apical effects of chronic exposure to two endocrine-active compounds and is the first standardized amphibian multiple life stage toxicity test to date. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Alterations of Global DNA Methylation and DNA Methyltransferase Expression in T and B Lymphocytes from Patients with Newly Diagnosed Autoimmune Thyroid Diseases After Treatment: A Follow-Up Study.

PubMed

Guo, Qingling; Wu, Dan; Yu, Huixin; Bao, Jiandong; Peng, Shiqiao; Shan, Zhongyan; Guan, Haixia; Teng, Weiping

2018-03-01

Dysregulated DNA methylation in lymphocytes has been linked to autoimmune disorders. The aims of this study were to identify global DNA methylation patterns in patients with autoimmune thyroid diseases and to observe methylation changes after treatment for these conditions. A cross-sectional study was conducted, including the following patients: 51 with newly diagnosed Graves' disease (GD), 28 with autoimmune hypothyroidism (AIT), 29 with positive thyroid autoantibodies, and 39 matched healthy volunteers. Forty GD patients treated with radioiodine or antithyroid drugs and 28 AIT patients treated with L-thyroxine were followed for three months. Serum free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibodies, thyroglobulin antibodies, and thyrotropin receptor antibodies were assayed using electrochemiluminescent immunoassays. CD3 + T and CD19 + B cells were separated by flow cytometry for total DNA and RNA extraction. Global DNA methylation levels were determined by absorptiometry using a methylation quantification kit. DNA methyltransferase (DNMT) expression levels were detected by real-time polymerase chain reaction. Hypomethylation and down-regulated DNMT1 expression in T and B lymphocytes were observed in the newly diagnosed GD patients. Neither the AIT patients nor the positive thyroid autoantibodies patients exhibited differences in their global DNA methylation status or DNMT mRNA levels compared with healthy controls. Antithyroid drugs restored global methylation and DNMT1 expression in both T and B lymphocytes, whereas radioiodine therapy affected only T cells. L-thyroxine replacement did not alter the methylation or DNMT expression levels in lymphocytes. The global methylation levels of B cells were negatively correlated with the serum thyroid peroxidase antibodies in patients with autoimmune thyroid diseases. Hyperthyroid patients with newly diagnosed GD had global hypomethylation and lower DNMT1 expression in T and B lymphocytes. The results provide the first demonstration that antithyroid drugs or radioiodine treatment restore global DNA methylation and DNMT1 expression with concurrent relief of hyperthyroidism.

Different tissue distribution, elimination, and kinetics of thyroxine and its conformational analog, the synthetic flavonoid EMD 49209 in the rat.

PubMed

Schröder-van der Elst, J P; van der Heide, D; Rokos, H; Köhrle, J; Morreale de Escobar, G

1997-01-01

The synthetic flavonoids EMD 23188 and EMD 49209, developed as T4 analogs, displace T4 from transthyretin, and in vitro they inhibit 5'-deiodinase activity. In vivo EMD 21388 causes tissue-specific changes in thyroid hormone metabolism. In tissues that are dependent on T3 locally produced from T4, total T3 was diminished. It was not known whether it was the presence of EMD interfering with 5'-deiodinase type II in tissues or the decreased T4 (substrate) availability that caused the lowered T3. To study whether the flavonoids enter tissues and, if this were the case, whether they enter tissues similarly, [125I]EMD 49209 together with [131I]T4 were injected into female rats and rats pretreated with EMD 21388. Tissues were extracted and submitted to HPLC. [125I]EMD 49209 disappeared quickly from plasma and enters peripheral tissues; peak values were reached after 0.25-0.5 h. Then [125I]EMD 49209 appeared in the intestines (after 6 h 40% of the dose). Tissue uptake of [131I]T4 was very rapid. EMD 21388 pretreatment caused an increase in the excretion of [125I]EMD 49209 into the intestines (40% after 0.25 h). The uptake of [131I]T4 increased, but not high enough to ensure normal tissue T4 concentrations. In the 5'-deiodinase type II-expressing tissues, no [125I]EMD 49209 could be detected. We conclude that the decrease in T3 locally produced from T4 is caused by the shortage of T4 as substrate and not to a direct effect of EMD on the activity of 5'-deiodinases I and II.

Effects of whole-body exposure to 915 MHz RFID on secretory functions of the thyroid system in rats.

PubMed

Kim, Hye Sun; Paik, Man-Jeong; Kim, Yeon Ju; Lee, Gwang; Lee, Yun-Sil; Choi, Hyung-Do; Kim, Byung Chan; Pack, Jeong-Ki; Kim, Nam; Ahn, Young Hwan

2013-10-01

As a part of an investigation on the potential risks of radiofrequency identification (RFID) on human health, we studied whether exposure to 915 MHz RFID in rats significantly affected the secretory function of the thyroid system. A reverberation chamber was used as a whole-body exposure system. Male Sprague-Dawley rats were exposed for 8 h per day, 5 days per week, for a duration of 2, 4, 8, or 16 weeks. The estimated whole-body average specific absorption rate (SAR) varied from 3.2 to 4.6 W/kg depending on the age/mass of the animals for the field of the 915 MHz RFID reader. Plasma levels of triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) were evaluated via enzyme-linked immunosorbent assay. Morphological changes in the thyroid gland were then analyzed. No changes in T3, T4, or TSH were observed over time between the sham- and RFID-exposed groups. We suggest that subchronic exposure to 915 MHz RFID at a SAR of 4 W/kg does not cause significant effects on thyroid secretory function. © 2013 Wiley Periodicals, Inc.

Circulating gluten-specific FOXP3+CD39+ regulatory T cells have impaired suppressive function in patients with celiac disease.

PubMed

Cook, Laura; Munier, C Mee Ling; Seddiki, Nabila; van Bockel, David; Ontiveros, Noé; Hardy, Melinda Y; Gillies, Jana K; Levings, Megan K; Reid, Hugh H; Petersen, Jan; Rossjohn, Jamie; Anderson, Robert P; Zaunders, John J; Tye-Din, Jason A; Kelleher, Anthony D

2017-12-01

Celiac disease is a chronic immune-mediated inflammatory disorder of the gut triggered by dietary gluten. Although the effector T-cell response in patients with celiac disease has been well characterized, the role of regulatory T (Treg) cells in the loss of tolerance to gluten remains poorly understood. We sought to define whether patients with celiac disease have a dysfunction or lack of gluten-specific forkhead box protein 3 (FOXP3) + Treg cells. Treated patients with celiac disease underwent oral wheat challenge to stimulate recirculation of gluten-specific T cells. Peripheral blood was collected before and after challenge. To comprehensively measure the gluten-specific CD4 + T-cell response, we paired traditional IFN-γ ELISpot with an assay to detect antigen-specific CD4 + T cells that does not rely on tetramers, antigen-stimulated cytokine production, or proliferation but rather on antigen-induced coexpression of CD25 and OX40 (CD134). Numbers of circulating gluten-specific Treg cells and effector T cells both increased significantly after oral wheat challenge, peaking at day 6. Surprisingly, we found that approximately 80% of the ex vivo circulating gluten-specific CD4 + T cells were FOXP3 + CD39 + Treg cells, which reside within the pool of memory CD4 + CD25 + CD127 low CD45RO + Treg cells. Although we observed normal suppressive function in peripheral polyclonal Treg cells from patients with celiac disease, after a short in vitro expansion, the gluten-specific FOXP3 + CD39 + Treg cells exhibited significantly reduced suppressive function compared with polyclonal Treg cells. This study provides the first estimation of FOXP3 + CD39 + Treg cell frequency within circulating gluten-specific CD4 + T cells after oral gluten challenge of patients with celiac disease. FOXP3 + CD39 + Treg cells comprised a major proportion of all circulating gluten-specific CD4 + T cells but had impaired suppressive function, indicating that Treg cell dysfunction might be a key contributor to disease pathogenesis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Comparison of circulating and intratumoral regulatory T cells in patients with renal cell carcinoma.

PubMed

Asma, Gati; Amal, Gorrab; Raja, Marrakchi; Amine, Derouiche; Mohammed, Chebil; Amel, Ben Ammar Elgaaied

2015-05-01

The clear evidence that tumor-infiltrating lymphocytes (TIL) exists in the tumor microenvironment raises the question why renal cell carcinoma (RCC) progresses. Numerous studies support the implication of CD4(+)CD25(high) regulatory T (Treg) cells in RCC development. We aimed in this study to characterize the phenotype and function of circulating and intratumoral Treg cells of RCC patient in order to evaluate their implication in the inhibition of the local antitumor immune response. Our results demonstrate that the proportion of Treg in TIL was, in average, similar to that found in circulating CD4(+) T cells of patients or healthy donors. However, intratumoral Treg exhibit a marked different phenotype when compared with the autologous circulating Treg. A higher CD25 mean level, HLA-DR, Fas, and GITR, and a lower CD45RA expression were observed in intratumoral Treg, suggesting therefore that these cells are effector in the tumor microenvironment. Additionally, intratumoral Treg showed a higher inhibitory function on autologous CD4(+)CD25(-) T cells when compared with circulating Treg that may be explained by an overexpression of FoxP3 transcription factor. These findings suggest that intratumoral Treg could be major actors in the impairment of local antitumor immune response for RCC patients.

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

Thyroid hormone levels in the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex.

PubMed Central

Tang, W W; Kaptein, E M

1989-01-01

Hypothalamic-pituitary dysfunction and thyroid gland cytomegalovirus inclusions have been described in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). We evaluated 80 patients with AIDS or ARC for the frequency of hypothalamic-pituitary or thyroid gland failure and altered serum thyroid hormone levels due to nonthyroidal disorders. One patient had subclinical hypothyroidism. Of these patients, 60% had low free triiodothyronine (T3) index values and 4% had low free thyroxine (T4) indexes; none of the latter had hypothalamic-pituitary or thyroid gland failure, since all serum cortisol values were greater than or equal to 552 nmol per liter (greater than or equal to 20 micrograms per dl) and all thyrotropin levels were less than or equal to 3 mU per liter (less than or equal to 3 microU per ml), respectively. Those who died had lower total T4 and T3, free T3 index, and albumin levels than those discharged from hospital. Serum total T4 and T3 levels correlated with albumin levels and total T3 with serum sodium levels. Serum total T3 levels best predicted the outcome of the hospital stay (accuracy = 82%). Thus, abnormal serum thyroid hormone levels in AIDS or ARC patients are most frequently due to nonthyroidal disorders, but hypothalamic-pituitary or thyroid gland failure may occur. PMID:2618039

[Hypothyroidism-when and how to treat?

PubMed

Koehler, V F; Reincke, M; Spitzweg, C

2018-06-05

The diagnosis of hypothyroidism is primarily based on clinical signs and symptoms as well as measurement of thyroid-stimulating hormone (TSH) concentration. Subclinical hypothyroidism is characterized by elevated TSH with normal serum free thyroxine (fT 4 ) and triiodothyronine (fT 3 ) levels, while in manifest hypothyroidism serum fT 4 and fT 3 levels are reduced. Common causes of primary hypothyroidism are autoimmune thyroiditis as well as therapeutic interventions, such as thyroid surgery or radioiodine therapy. Signs and symptoms of hypothyroidism include fatigue, bradycardia, constipation and cold intolerance. In subclinical hypothyroidism, symptoms may be absent. Initiation of levothyroxine (T 4 ) therapy not only depends on the level of TSH elevation, but also on other factors, such as patient age, presence of pregnancy or comorbidities. Treatment of patients with subclinical hypothyroidism is still a controversial topic. In general, thyroid hormone replacement therapy in non-pregnant adults ≤ 70 years is clearly indicated if the TSH concentration is >10 mU/l. Standard of care for treatment of hypothyroidism is T 4 monotherapy. The biochemical treatment goal for T 4 replacement in primary hypothyroidism is a TSH level within the reference range (0.4-4.0 mU/l). In contrast, in secondary hypothyroidism, serum fT 4 levels are the basis for adjusting thyroid hormone dosage. Inadequate replacement of T 4 resulting in subclinical or even manifest hyperthyroidism should urgently be avoided. T 4 /liothyronine (T3) combination therapy is still a matter of debate and not recommended as standard therapy, but may be considered in patients with persistence of symptoms, despite optimal T 4 treatment, based on expert opinion.

The effect of Persian shallot (Allium hirtifolium Boiss.) extract on blood sugar and serum levels of some hormones in diabetic rats.

PubMed

Mehdi, Mahmoodi; Javad, Hosseini; Seyed-Mostafa, Hosseini-Zijoud; Mohammadreza, Mirzaee; Ebrahim, Mirzajani

2013-03-01

Diabetes mellitus (DM) is caused by hyperglycemia, resulting from defective insulin secretion or function. It is widely believed that the antioxidant micronutrients obtained from plants afford significant protection against diseases like diabetes mellitus. Present study was aimed to examine the effects of Persian shallot (Allium hirtifolium Boiss) on FBS, HbA1c, insulin, triiodothyronine (T3) and thyroxine (T4) levels in type 1 diabetic rats. Thirty two male Wistar rats were divided into 4 groups of 8. The diabetic groups received 100 and 200 mg/kg Persian shallot extract, diabetic control and normal control received %0.9 saline for 30 days. At the end of treatments, fasting blood specimens were collected. The levels of FBS, HbA1c, insulin, T3 and T4 were measured. Our findings indicated that hydroalcoholic extract of Persian shallot significantly decreased serum levels of FBS and HbA1c in treated groups (in a dose dependent manner) (p<0.05). The serum levels of insulin and T3 slightly increased by Persian shallot but the T4 serum level was declined. These beneficial effects of Persian shallot extracts in diabetic rats could probably be due to the antioxidant capacity of its phenolic and diallyl disulfide content.

Evaluation of recombinant human thyroid-stimulating hormone to test thyroid function in dogs suspected of having hypothyroidism.

PubMed

Boretti, Felicitas S; Sieber-Ruckstuhl, Nadja S; Favrot, Claude; Lutz, Hans; Hofmann-Lehmann, Regina; Reusch, Claudia E

2006-12-01

To evaluate the use of recombinant human (rh) thyroid-stimulating hormone (TSH) in dogs with suspected hypothyroidism. 64 dogs with clinical signs of hypothyroidism. Dogs received rhTSH (75 microg/dog, IV) at a dose independent of their body weight. Blood samples were taken before and 6 hours after rhTSH administration for determination of total serum thyroxine (T(4)) concentration. Dogs were placed into 1 of 3 groups as follows: those with normal (ie, poststimulation values indicative of euthyroidism), unchanged (ie, poststimulation values indicative of hypothyroidism; no thyroid gland stimulation), or intermediate (ie, poststimulation values between unchanged and normal values) post-TSH T(4) concentrations. Serum canine TSH (cTSH) concentration was determined in prestimulation serum (ie, before TSH administration). 14, 35, and 15 dogs had unchanged, normal, and intermediate post-TSH T(4) concentrations, respectively. Basal T(4) and post-TSH T(4) concentrations were significantly different among groups. On the basis of basal serum T(4) and cTSH concentrations alone, 1 euthyroid (normal post-TSH T(4), low basal T(4), and high cTSH concentrations) and 1 hypothyroid dog (unchanged post-TSH T(4) concentration and low to with-in reference range T(4) and cTSH concentrations) would have been misinterpreted as hypothyroid and euthyroid, respectively. Nine of the 15 dogs with intermediate post-TSHT(4) concentrations had received medication known to affect thyroid function prior to the test, and 2 of them had severe nonthyroidal disease. The TSH-stimulation test with rhTSH is a valuable diagnostic tool to assess thyroid function in selected dogs in which a diagnosis of hypothyroidism cannot be based on basal T(4) and cTSH concentrations alone.

Type 1 5'-deiodinase activity is inhibited by oxidative stress and restored by alpha-lipoic acid in HepG2 cells.

PubMed

Chen, Kanjun; Yan, Biao; Wang, Fei; Wen, Feiting; Xing, Xingan; Tang, Xue; Shi, Yonghui; Le, Guowei

2016-04-08

3,3',5-triiodothyronine (T3) is largely generated from thyroxine (T4) by the catalysis of deiodinases in peripheral tissues. Emerging evidences have indicated its broad participation in regulating various metabolic process via protecting tissues from oxidative stress and improving cellular antioxidant capacity. However, the potential correlation between the oxidative stress and conversion of T4 to T3 is still unclear. In the present study, the effects of T3 and T4 on redox homeostasis in HepG2 cells pre-treated with H2O2 was investigated. It revealed that T3 significantly rescued the apoptotic cell death, consistent with an upregulation of cell antioxidant ability and reduction of ROS accumulation while T4 did not. Afterwards, we examined the enzyme activity and mRNA expression of type 1 5'-deiodianse (DIO1), T3 and rT3 level and found that H2O2 reduced both DIO1 activity and expression in a dose-dependent manner, which consequently declined T3 and rT3 generation. Alpha-lipoic acid (LA) treatment notably restored DIO1 activity, T3 and rT3 level, as well as transcriptional abnormalities of inflammation-associated genes. It suggests that oxidative stress may reduce DIO1 activity by an indirect way like activating cellular inflammatory responses. All these results indicate that the oxidative stress downregulates the conversion of T4 to T3 through DIO1 function in HepG2 cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical significance of circulating immune cells in left- and right-sided colon cancer.

PubMed

Di, Jiabo; Zhuang, Meng; Yang, Hong; Jiang, Beihai; Wang, Zaozao; Su, Xiangqian

2017-01-01

Left-sided and right-sided colon cancers (LCCs and RCCs, respectively) differ in their epidemiology, pathogenesis, genetic and epigenetic alterations, molecular pathways and prognosis. Notably, immune response gene expression profiles have been shown to differ between patients with LCC and patients with RCC. The immune system plays an important role in tumor immunosurveillance, and there is increasing evidence that peripheral blood immune cells have a profound influence on tumor prognosis. This study aimed to determine the clinical significance of circulating immune cells with respect to colon tumor locations. Different types of circulating immune cells were separated and analysed based on their surface markers by flow cytometry. We compared the numbers of dendritic cells (DCs) and T cell subsets in the peripheral blood of 94 patients with RCC or LCC and analysed the proportions of these immune cells in relation to tumor stage, tumor differentiation and lymphatic metastasis. We show that at later tumor stages, patients with LCC had higher levels of circulating myeloid DCs ( P  = 0.049) and plasmacytoid DCs ( P  = 0.018) than patients with RCC. In poorly differentiated tumors, LCC patients had significantly higher amount of plasmacytoid DCs ( P  = 0.036), CD4 + memory T (Tm) cells ( P  = 0.012), CD4 + T cells ( P  = 0.028), Tm cells ( P  = 0.014), and regulatory T cells ( P  = 0.001) than RCC patients. The levels of circulating CD4 + T cells, Tm cells and CD4 + Tm cells were significantly elevated at later stages in patients with LCC or RCC, while these cells decreased in poorly differentiated tumors in patients with RCC. Moreover, CD4 + Tm cell and CD4 + T cell levels are significantly associated with lymph node metastasis in patients with LCC and RCC. Circulating immune cells were associated with tumor location, tumor stage and tumor differentiation, and can be used to predict lymphatic metastasis in patients with colon cancer. This variation in systemic immunity could contribute to the differential prognosis of patients with colon cancer.

Placenta hominis protects osteoporosis in ovariectomized rats.

PubMed

Chae, H J; Choi, K H; Chae, S W; Kim, H M; Shin, T K; Lee, G Y; Jeong, G S; Park, H R; Choi, H I; Kim, S B; Yoo, S K; Kim, H R

2006-01-01

In China, Japan, and Korea, placenta hominis extracts (PHEs) are used clinically for the treatment of osteoporosis. The anti-osteoporotic effect of PHEs was studied. The trabecular bone area and thickness in OVX rats decreased by 50% from those in sham-operated rats; these decreases were completely inhibited by administration of PHEs for 7 weeks. Osteoclast numbers and the osteoblast surface were enhanced in OVX rats, but PHEs had no effect on these phenomena. Serum phosphorus and alkaline phosphatase in OVX rats increased compared to those in sham-operated rats, but the increases were not affected by the administration of PHEs. Thyroxine (T4) level was stimulated in OVX rats. The extracts inhibited the T4 level in the OVX rats. These results strongly suggest that PHEs be effective in preventing the development of bone loss induced by OVX in rats.

Physiopathological effects of the administration of chronic cyanide to growing goats--a model for ingestion of cyanogenic plants.

PubMed

Soto-Blanco, B; Górniak, S L; Kimura, E T

2001-07-01

Ingestion of cyanogenic plants, such as cassava and sorghum, has been associated with goitre and tropical pancreatic diabetes in both humans and animals. Thus, the objective of the present study was to determine the toxic effects on the thyroid and pancreas in growing goats of prolonged exposure to potassium cyanide (KCN). Thirty-four male goats were divided into five groups dosed with KCN at 0 (control). 0.3, 0.6, 1.2 or 3.0 mg/kg daily for 5 months. Blood samples were obtained in order to determine the glucose, cholesterol, thyroxine (T4), triiodothyronine (T3) and thiocyanate concentrations and for haematological studies; pancreas and thyroid gland were collected for histopathological study. The group receiving the highest dose of cyanide showed lower body weight gains and carcase weights and a decrease in plasma T3 concentrations compared to the control group. Reabsorption vacuoles in follicular colloid and normocytic normochromic anaemia were observed in the experimental animals. Inhibition of peripheral conversion of T4 to T3 is suggested. However, no diabetogenic effects were observed.

Non-invasive measurement of thyroid hormone in feces of a diverse array of avian and mammalian species.

PubMed

Wasser, Samuel K; Azkarate, Jurgi Cristòbal; Booth, Rebecca K; Hayward, Lisa; Hunt, Kathleen; Ayres, Katherine; Vynne, Carly; Gobush, Kathleen; Canales-Espinosa, Domingo; Rodríguez-Luna, Ernesto

2010-08-01

We developed and validated a non-invasive thyroid hormone measure in feces of a diverse array of birds and mammals. An I(131) radiolabel ingestion study in domestic dogs coupled with High Pressure Liquid Chromatography (HPLC) analysis, showed that peak excretion in feces occurred at 24-48h post-ingestion, with I(131)-labelled thyroid hormone metabolites excreted primarily as triiodothyronine (T3) and relatively little thyroxine (T4), at all excretion times examined. The immunoreactive T3 profile across these same HPLC fractions closely corresponded with the I(131) radioactive profile. By contrast, the T4 immunoreactive profile was disproportionately high, suggesting that T4 excretion included a high percentage of T4 stores. We optimized and validated T3 and T4 extraction and assay methods in feces of wild northern spotted owls, African elephants, howler monkeys, caribou, moose, wolf, maned wolf, killer whales and Steller sea lions. We explained 99% of the variance in high and low T3 concentrations derived from species-specific sample pools, after controlling for species and the various extraction methods tested. Fecal T3 reflected nutritional deficits in two male and three female howler monkeys held in captivity for translocation from a highly degraded habitat. Results suggest that thyroid hormone can be accurately and reliably measured in feces, providing important indices for environmental physiology across a diverse array of birds and mammals. Copyright 2010 Elsevier Inc. All rights reserved.

Effect of an anti-inflammatory dose of prednisone on thyroid hormone monitoring in hypothyroid dogs.

PubMed

O'Neill, Sarah H; Frank, Linda A; Reynolds, Lisa M

2011-04-01

It is not uncommon for a hypothyroid dog to be receiving concurrent corticosteroids. As hypothyroid dogs receiving thyroid supplement need periodic monitoring, knowledge of whether prednisone alters thyroid hormone concentrations would be useful to determine whether testing can or should be done while the dog is receiving therapy and whether dose adjustments are appropriate. In this study, the effect of short-term anti-inflammatory prednisone was determined in dogs with naturally occurring hypothyroidism. Eight adult dogs were given prednisone (1.0 mg/kg, orally) daily for 7 days and then on alternate days for 14 days. Serum total thyroxine (T(4) ), free T(4) (fT(4) ), and thyroid-stimulating hormone (TSH) were measured on days 7, 21 and 28 and compared with baseline data. Total T(4) concentrations were significantly decreased after 7 days of anti-inflammatory prednisone, but were not significantly altered from baseline on days 21 or 28. Free T(4) and TSH concentrations were not significantly altered from baseline at any point during the study. Two dogs had decreased total T(4) concentrations on day 7, which may have resulted in an alteration in thyroid supplementation. Results showed that administration of prednisone at a dosage of 1 mg/kg, orally, once daily for 7 days decreased total T(4) , while fT(4) was unchanged, suggesting that fT(4) may be less affected by daily prednisone administration. Anti-inflammatory doses of prednisone administered every other day did not interfere with thyroid hormone monitoring. © 2010 The Authors. Journal compilation © 2010 ESVD and ACVD.

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.

The Change of Left Ventricular Function in Rats with Subclinical Hypothyroid and the Effects of Thyroxine Replacement.

PubMed

Chen, Xuedi; Gao, Cuixia; Gong, Ningning; Wang, Yu; Tian, Limin

2018-01-01

The main purpose of this study was to explore the relationships between serca2a, Ryr2, adipokines, and the left ventricular function in the subclinical hypothyroidism with different TSH levels and to determine the impact of L-T4 treatment on these indexes. Sixty-five male Wistar rats were randomly divided into five groups: control group; sHT A, B, and C group; and sHT + T4 group. The sHT rats were induced by methimazole (MMI), and the sHT + T4 rats were administered with L-T4 treatment after 8 weeks of MMI administration. Serum TT4, TSH, APN, chemerin, and TNF- α were detected by radioimmunoassay kits and ELISA kits; left ventricular function was measured by PowerLab system via subclavian artery catheter. The expression of Serca2a, Ryr2, APN, chemerin, and TNF- α were detected by RT-PCR, Western blot, and immunohistochemistry. The sHT groups had significantly higher TSH, chemerin, and TNF- α and lower Serca2a, Ryr2, and APN. The left ventricular pressure and heart rate in sHT groups were significantly lower in control and sHT + T4 group. Histopathological examination revealed the pathological changes in the sHT rats' heart. L-T4 administration reduced TSH level and improved left ventricular function. TSH can impair left ventricular function by regulating several factors, and L-T4 treatment ameliorates it in sHT rats.

Subunit vaccine H56/CAF01 induces a population of circulating CD4 T cells that traffic into the Mycobacterium tuberculosis-infected lung.

PubMed

Woodworth, J S; Cohen, S B; Moguche, A O; Plumlee, C R; Agger, E M; Urdahl, K B; Andersen, P

2017-03-01

The capacity of CD4 T cells to protect against Mycobacterium tuberculosis (Mtb) is governed by their ability to localize to the lung site of infection. Subunit vaccine H56/CAF01, a liposome-adjuvanted fusion protein of Mtb antigens Ag85B, ESAT-6, and Rv2660, conferred durable protection and elicited polyfunctional CD4 T cells that preferentially localized to the lung parenchyma. These lung-resident T cells had reduced KLRG1 and increased CXCR3 expression, an intermediate state of Th1 differentiation that has been associated with Mtb protection. Importantly, KLGR1 - CXCR3 + cells were also enriched in the lung vasculature and peripheral circulation of vaccinated animals, but not controls. Moreover, S1P1R blockade rapidly cleared this population from the blood and adoptive transfer of T cells recovered from the vasculature of vaccinated, but not control, mice efficiently trafficked into the Mtb-infected lung parenchyma. Thus, durable immunity elicited by H56/CAF01 vaccination is associated with the maintenance of circulating CD4 T cells that selectively home to the lung parenchyma.

Multicompartmental model for iodide, thyroxine, and triiodothyronine metabolism in normal and spontaneously hyperthyroid cats

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

Hays, M.T.; Broome, M.R.; Turrel, J.M.

A comprehensive multicompartmental kinetic model was developed to account for the distribution and metabolism of simultaneously injected radioactive iodide (iodide*), T3 (T3*), and T4 (T4*) in six normal and seven spontaneously hyperthyroid cats. Data from plasma samples (analyzed by HPLC), urine, feces, and thyroid accumulation were incorporated into the model. The submodels for iodide*, T3*, and T4* all included both a fast and a slow exchange compartment connecting with the plasma compartment. The best-fit iodide* model also included a delay compartment, presumed to be pooling of gastrosalivary secretions. This delay was 62% longer in the hyperthyroid cats than in themore » euthyroid cats. Unexpectedly, all of the exchange parameters for both T4 and T3 were significantly slowed in hyperthyroidism, possibly because the hyperthyroid cats were older. None of the plasma equivalent volumes of the exchange compartments of iodide*, T3*, or T4* was significantly different in the hyperthyroid cats, although the plasma equivalent volume of the fast T4 exchange compartments were reduced. Secretion of recycled T4* from the thyroid into the plasma T4* compartment was essential to model fit, but its quantity could not be uniquely identified in the absence of multiple thyroid data points. Thyroid secretion of T3* was not detectable. Comparing the fast and slow compartments, there was a shift of T4* deiodination into the fast exchange compartment in hyperthyroidism. Total body mean residence times (MRTs) of iodide* and T3* were not affected by hyperthyroidism, but mean T4* MRT was decreased 23%. Total fractional T4 to T3 conversion was unchanged in hyperthyroidism, although the amount of T3 produced by this route was increased nearly 5-fold because of higher concentrations of donor stable T4.« less

Optimizing treatment of hypothyroidism.

PubMed

Clarke, Nick; Kabadi, Udaya M

2004-01-01

Several thyroid hormone preparations are currently available, including levothyroxine sodium (thyroxine), liothyronine (triiodothyronine), and desiccated thyroid extract, as well as a combination of levothyroxine sodium and liothyronine. Levothyroxine sodium monotherapy at an appropriate daily dose provides uniform levels of both thyroxine and triiodothyronine in the circulation without diurnal variation. Therefore, it is the preparation of choice in most patients with hypothyroidism of both the primary and central types. A normal thyrotropin (TSH) level of 1-2 mU/L is considered the determinant of optimal daily levothyroxine sodium dose in patients with primary hypothyroidism, whereas normal thyroxine and triiodothyronine levels in the mid or upper normal range may denote optimal replacement in patients with central hypothyroidism. Optimal daily levothyroxine sodium dose may be determined according to serum TSH level at the time of diagnosis of primary hypothyroidism. Initial administration of close to the full calculated dose of levothyroxine sodium is appropriate for younger patients, reducing the need for follow-up visits and repeated laboratory testing for dose titration. In the elderly and in patients with a history of coronary artery disease (CAD), the well established approach of starting with a low dose and gradually titrating to the full calculated dose is always the best option. Levothyroxine sodium can and should be continued in patients receiving treatment for CAD. Even minor over-replacement during initial titration of levothyroxine sodium should be avoided, because of the risk of cardiac events. Chronic over-replacement may induce osteoporosis, particularly in postmenopausal women, and should also be avoided.

Circulating precursor CCR7(lo)PD-1(hi) CXCR5⁺ CD4⁺ T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure.

PubMed

He, Jing; Tsai, Louis M; Leong, Yew Ann; Hu, Xin; Ma, Cindy S; Chevalier, Nina; Sun, Xiaolin; Vandenberg, Kirsten; Rockman, Steve; Ding, Yan; Zhu, Lei; Wei, Wei; Wang, Changqi; Karnowski, Alexander; Belz, Gabrielle T; Ghali, Joanna R; Cook, Matthew C; Riminton, D Sean; Veillette, André; Schwartzberg, Pamela L; Mackay, Fabienne; Brink, Robert; Tangye, Stuart G; Vinuesa, Carola G; Mackay, Charles R; Li, Zhanguo; Yu, Di

2013-10-17

Follicular B helper T (Tfh) cells support high affinity and long-term antibody responses. Here we found that within circulating CXCR5⁺ CD4⁺ T cells in humans and mice, the CCR7(lo)PD-1(hi) subset has a partial Tfh effector phenotype, whereas CCR7(hi)PD-1(lo) cells have a resting phenotype. The circulating CCR7(lo)PD-1(hi) subset was indicative of active Tfh differentiation in lymphoid organs and correlated with clinical indices in autoimmune diseases. Thus the CCR7(lo)PD-1(hi) subset provides a biomarker to monitor protective antibody responses during infection or vaccination and pathogenic antibody responses in autoimmune diseases. Differentiation of both CCR7(hi)PD-1(lo) and CCR7(lo)PD-1(hi) subsets required ICOS and BCL6, but not SAP, suggesting that circulating CXCR5⁺ helper T cells are primarily generated before germinal centers. Upon antigen reencounter, CCR7(lo)PD-1(hi) CXCR5⁺ precursors rapidly differentiate into mature Tfh cells to promote antibody responses. Therefore, circulating CCR7(lo)PD-1(hi) CXCR5⁺ CD4⁺ T cells are generated during active Tfh differentiation and represent a new mechanism of immunological early memory. Copyright © 2013 Elsevier Inc. All rights reserved.

Follow-up of newborns of mothers with Graves' disease.

PubMed

Levy-Shraga, Yael; Tamir-Hostovsky, Liran; Boyko, Valentina; Lerner-Geva, Liat; Pinhas-Hamiel, Orit

2014-06-01

Overt neonatal Graves' disease is rare, but may be severe, even life threatening, with deleterious effects on neural development. The main objective of this study was to describe the course of thyrotropin (TSH) and free thyroxin (fT4) levels, as well as postnatal weight gain in relation to fT4 levels, in neonates born to women with Graves' disease without overt neonatal thyrotoxicosis. Such information is important to deduce the optimal schedule for evaluation. We conducted a retrospective chart review of neonates born to mothers with Graves' disease between January 2007 and December 2012. The records were reviewed for sex, gestational age, birth weight, maternal treatment during pregnancy, and maternal thyroid stimulating immunoglobulin (TSI) level. For each visit in the clinic, the data included growth parameters, presence of symptoms suspected for hyperthyroidism, blood test results (levels of TSH, fT4, and TSI), and treatment. Ninety-six neonates were included in the study (49 males), with a total of 320 measurements of thyroid function tests (TSH and fT4). Four neonates (4%) had overt neonatal Graves' disease; one of them along with nine others were born preterm. In 77 (92.9%) of the remaining 83 neonates (the subclinical group), fT4 levels were above the 95th percentile on day 5. All had normal fT4 on day 15. A negative association was found between fT4 and weight gain during the first two weeks. In this cohort, most neonates born to mothers with Graves' disease had a subclinical course with abnormal fT4 levels that peaked at day 5. After day 14, all measurements of fT4 returned to the normal range, although measurements of TSH remained suppressed for up to three months. Elevated fT4 was associated with poor weight gain.

tPA-MMP-9 Axis Plays a Pivotal Role in Mobilization of Endothelial Progenitor Cells from Bone Marrow to Circulation and Ischemic Region for Angiogenesis

PubMed Central

Day, Yuan-Ji

2016-01-01

We examined the role of tissue plasminogen activator- (tPA-) matrix metalloproteinase- (MMP-) 9 in mobilizing endothelial progenitor cells (EPCs) from bone marrow to circulation and critical limb ischemia (CLI) region. Male C57BL/6J mice having been irradiated were categorized into wild-type mice (WT) receiving WT bone marrow cell (BMC) transfusion (group 1), WT mice receiving MMP-9 knockout (MMP-9−/−) BMC (group 2), MMP-9−/− receiving MMP-9−/− BMC (group 3), and MMP-9−/− receiving WT BMC (group 4), each of which was subdivided into sham control (SC), CLI, SC-tPA, and CLI-tPA. In groups 1 and 4, by post-CLI 18 h and day 14, circulating EPC (C-kit+/CD31+, Sca-1+/KDR+) levels were highest in CLI-tPA subgroup. In groups 2 and 3, EPC levels did not differ among all subgroups. The EPC levels in bone marrow were higher in groups 2 and 3 than those in groups 1 and 4. By day 14, in animals with CLI, expression levels of proangiogenic factors (CXCR4, SDF-1α, and VEGF) showed similar trends as circulating EPC levels. Moreover, the number of infiltrated neutrophils and macrophages in quadriceps was higher in groups 1 and 4 than groups in 2 and 3. In conclusion, tPA-MMP-9 axis plays a crucial role in EPC mobilization and angiogenesis in experimental CLI. PMID:27610138

Persistence of a circadian rhythmicity for thyroid hormones in plasma and thyroid of hibernating male Rana ridibunda.

PubMed

Kühn, E R; Delmotte, N M; Darras, V M

1983-06-01

The presence and circadian rhythmicity of thyroid hormones was studied in plasma and the thyroid gland of male Rana ridibunda before and during hibernation. Hibernating January frogs do have a lower T3 and T4 content of their thyroid gland whereas plasma levels of T3 are maintained and of T4 increased compared to fed September or October frogs. It seems likely that the increased photoperiod in January will be responsible for this increased T4 secretion, since controlled laboratory experiments performed in December did not reveal any influence of low temperature on circulating T3 or T4 levels. Also feeding does not influence circulating levels and thyroid content of thyroid hormones in frogs kept at room temperature during the month of January. A circadian rhythmicity of T3 and T4 in the thyroid gland is present in fed October frogs and in non fed December frogs acclimated at 5 degrees C for 12 days with an acrophase for T3 at approximately 1500 h and for T4 at around 1900 h, whereas in plasma only T3 does have circadian variations (acrophase about midnight) but not T4. When December frogs are acclimated to room temperature for 12 days, frogs are active again, but do not eat and have a lower body weight than frogs hibernating at 5 degrees C. Their T3 content of the thyroid gland has disappeared, but T4 thyroid content and plasma levels of T3 and T4 are maintained. As in hibernating frogs, no circadian variations in T4 plasma concentrations are present whereas the circadian thyroid T4 rhythm disappears. At the same time a dampening in rhythmicity for plasma T3 as judged by the significantly lower amplitude occurs. It is concluded that the persistence of circulating levels of thyroid hormones and of a circadian cyclicity for T3 in plasma in non feeding hibernating frogs may reflect the special metabolic state e.g. availability of food reserves in these animals.

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

PubMed

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

2018-01-01

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

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

PubMed

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

1990-01-01

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

Effects of long-term oral administration of levothyroxine sodium on serum thyroid hormone concentrations, clinicopathologic variables, and echocardiographic measurements in healthy adult horses.

PubMed

Frank, Nicholas; Buchanan, Benjamin R; Elliott, Sarah B

2008-01-01

To determine the effects of long-term oral levothyroxine sodium (L-T(4)) administration on serum thyroid hormone concentrations, thyroid gland function, clinicopathologic variables, and echocardiographic examination measurements in adult euthyroid horses. 6 healthy adult mares. Horses received L-T(4) (48 mg/d) orally for 48 weeks. Every 4 weeks, physical examinations were performed; blood samples were collected for CBC, plasma biochemical analyses, and assessments of serum total triiodothyronine (tT(3)) and thyroxine (tT(4)) concentrations. Plasma creatine kinase MB activity and cardiac troponin I concentration were also measured. Echocardiographic examinations were performed before and at 16, 32, and 48 weeks during the treatment period. During the treatment period, mean body weight decreased significantly; heart rate varied significantly, but the pattern of variation was not consistent. Significant time effects were detected for certain clinicopathologic variables, but mean values remained within reference ranges. Cardiac troponin I was only detectable in 8 of 24 plasma samples (concentration range, 0.01 to 0.03 ng/mL). Serum creatine kinase MB activity did not change significantly over time. Compared with the pretreatment value, 5.4-, 4.0-, and 3.7-fold increases in mean serum tT(4) concentrations were detected at 16, 32, and 48 weeks, respectively. Some cardiac measurements changed significantly over time, but mean values remained within published reference ranges. Mean fractional shortening was lower than the pretreatment mean value at 16 and 32 weeks. In horses, long-term oral administration of 48 mg of L-T(4)/d significantly increased serum tT(4) concentrations and did not appear to adversely affect health.

Paediatric reference interval and biological variation trends of thyrotropin (TSH) and free thyroxine (T4) in an Asian population.

PubMed

Loh, Tze Ping; Sethi, Sunil Kumar; Metz, Michael Patrick

2015-08-01

To describe the reference intervals and biological variation data for thyrotropin (TSH) and free thyroxine (FT4) in a mixed Asian population using an indirect sampling approach and to compare them with published reports. TSH and FT4 of children measured once or twice over a 7-year period (2008-2014) at primary-care and tertiary-care settings were extracted from the laboratory information system. After excluding outliers, age-related reference intervals were derived using the Lambda-Mu-Sigma (LMS) approach, while age-partitioned biological variation data were obtained according to recommendations by Fraser and Harris. Both TSH and FT4 were very high at birth and declined with age. Similarly within-individual and between-individual biological variations were higher for both TSH and FT4 at birth and also declined with age. Our data were broadly similar to previous studies. Significant heterogeneity in study population and methods prohibited direct numerical comparison between this and previously published studies. This study fills two important gaps in our knowledge of paediatric thyroid function by reporting the centile trends (and reference values) in a mixed Asian population, as well as providing age-partitioned biological variation data. The variation in published reference intervals highlights the difficulty in harmonising paediatric thyroid reference intervals or recommending universal clinical cut-offs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The reference intervals of thyroid stimulating hormone in healthy individuals with normal levels of serum free thyroxine and without sonographic pathologies.

PubMed

Kutluturk, Faruk; Yildirim, Beytullah; Ozturk, Banu; Ozyurt, Huseyin; Bekar, Ulku; Sahin, Semsettin; Akturk, Yeliz; Akbas, Ali; Cetin, Ilhan; Etikan, Ilker

2014-01-01

The aim of the present study was to investigate the reference intervals for thyroid stimulating hormone (TSH) in healthy individuals with normal levels of serum free thyroxine (fT4) and without sonographic pathologies, and determine the effects of age, gender, and residence on the TSH reference intervals. This research was a population-based study conducted in 70 regions. The random sampling method was used to select the 1095 subjects of the study among inhabitants aged 18 and above. Patients who had a previous history of thyroid disease and had been taking medication were excluded from the study as this may have affected their fT4 or TSH levels. In addition, subjects who had serum fT4 without a reference range and abnormal ultrasonography findings were also excluded. A total of 408 subjects were used for establishing the reference intervals for TSH. The data for TSH in the study group were not normally distributed according to the Kolmogorov-Smirnov index. The geometric mean was 1.62 mIU/L, the median was 1.40 mIU/L, and the 95% reference intervals were 0.38-4.22 mIU/L. The median TSH level was higher in females compared to males (p < 0.05). In the female subjects 2.5th percentile of TSH was lower and 97.5th percentile was higher than those of males. The reference intervals of TSH were of lower values in subjects over 50 years old (p < 0.001). Studies suggest that determination of the TSH reference intervals may differ due to environmental influences or due to age, gender, and race. It is suggested that the lower limit of normal TSH for the adult Turkish population would be 0.38 mIU/L and the upper limit similar to the traditional value of 4.2 mIU/L. If each clinician uses their population-specific reference interval for TSH, thyroid function abnormalities can be accurately estimated.

Exposure to pyrethroids insecticides and serum levels of thyroid-related measures in pregnant women

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

Zhang, Jie; Hisada, Aya; Yoshinaga, Jun, E-mail: junyosh@k.u-tokyo.ac.jp

Possible association between environmental exposure to pyrethroid insecticides and serum thyroid-related measures was explored in 231 pregnant women of 10–12 gestational weeks recruited at a university hospital in Tokyo during 2009–2011. Serum levels of free thyroxine (fT4), thyroid stimulating hormone (TSH) and thyroid biding globulin (TBG) and urinary pyrethroid insecticide metabolite (3-phenoxybenzoic acid, 3-PBA) were measured. Obstetrical information was obtained from medical records and dietary and lifestyle information was collected by self-administered questionnaire. Geometric mean concentration of creatinine-adjusted urinary 3-PBA was 0.363 (geometric standard deviation: 3.06) μg/g cre, which was consistent with the previously reported levels for non-exposed Japanese adultmore » females. The range of serum fT4, TSH and TBG level was 0.83–3.41 ng/dL, 0.01–27.4 μIU/mL and 16.4–54.4 μg/mL, respectively. Multiple regression analysis was carried out by using either one of serum levels of thyroid-related measures as a dependent variable and urinary 3-PBA as well as other potential covariates (age, pre-pregnancy BMI, parity, urinary iodine, smoking and drinking status) as independent variables: 3-PBA was not found as a significant predictor of serum level of thyroid-related measures. Lack of association may be due to lower pyrethroid insecticide exposure level of the present subjects. Taking the ability of pyrethroid insecticides and their metabolite to bind to nuclear thyroid hormone (TH) receptor, as well as their ability of placental transfer, into consideration, it is warranted to investigate if pyrethroid pesticides do not have any effect on TH actions in fetus brain even though maternal circulating TH level is not affected. -- Highlights: • Pyrethroid exposure and thyroid hormone status was examined in pregnant women. • Urinary 3-phenoxybenzoic acid was used as a biomarker of exposure. • Iodine nutrition, age and other covariates were included in statistical models. • No association was found between levels of thyroid hormone and pyrethroid exposure. • The result may be ascribed to lower exposure level.« less

Effects of polychlorinated biphenyl (PCB) on regulation of thyroid-, growth-, and neurochemically related developmental processes in young rats

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

Juarez de Ku, L.M.

1992-01-01

Neonatal exposure to the toxic chemical polychlorinated biphenyl (PCB) induces hypothyroidism and retarded growth. Neonatal rats made hypothyroid by chemical or surgical means experience retarded growth and subnormal activity of choline acetyltransferase (ChAT) This study compared thyroid-, growth-, and neurochemically-related processes altered by hypothyroidism induced by other means, with PCB-induced hypothyroidism: (1) titers of thyroid stimulating hormone (TSH); (2) titers of hormones that regulate growth [growth hormone (GH), insulin-growth like factor-I (IGF-1), growth hormone releasing hormone (GHRH) and somatostatin (SS)]; or (3) brain ChAT activity. Whether PCB-induced growth retardation and other alterations are secondary to accompanying hypothyroidism rather than ormore » in addition to a direct effect of PCB was also examined. Pregnant rats were fed chow containing 0 (controls), 62.5, 125, or 250 ppm PCB (entering offspring through placenta and milk) throughout pregnancy and lactation. Neonates exposed to PCB displayed many alterations similar to those made hypothyroid by other means: depression of overall and skeletal growth, circulating by other means: depression of overall and skeletal growth, circulating T[sub 4] levels and ChAT activity, and no change in hypothalamic GHRH and SS concentrations. Differences included a paradoxical increase in circulating GH levels, and no significant alteration of circulation IGF-1 and TSH levels and pituitary GH and TSH levels (although trends were in the expected direction). Thus, PCB-induced hypothyroidism may partially cause altered skeletal growth, circulating GH and TSH concentrations, and ChAT activity. Both T[sub 4] and T[sub 3] injections returned circulating TSH and GH levels and pituitary TSH content toward control levels; T[sub 3] restored skeletal, but not overall growth; and T[sub 4] elevated ChAT activity.« less

Skin-resident CD4+ T cells protect against Leishmania major by recruiting and activating inflammatory monocytes

PubMed Central

Glennie, Nelson D.; Volk, Susan W.

2017-01-01

Tissue-resident memory T cells are required for establishing protective immunity against a variety of different pathogens, although the mechanisms mediating protection by CD4+ resident memory T cells are still being defined. In this study we addressed this issue with a population of protective skin-resident, IFNγ-producing CD4+ memory T cells generated following Leishmania major infection. We previously found that resident memory T cells recruit circulating effector T cells to enhance immunity. Here we show that resident memory CD4+ T cells mediate the delayed-hypersensitivity response observed in immune mice and provide protection without circulating T cells. This protection occurs rapidly after challenge, and requires the recruitment and activation of inflammatory monocytes, which limit parasites by production of both reactive oxygen species and nitric oxide. Overall, these data highlight a novel role for tissue-resident memory cells in recruiting and activating inflammatory monocytes, and underscore the central role that skin-resident T cells play in immunity to cutaneous leishmaniasis. PMID:28419151

Establishing a reference range for triiodothyronine levels in preterm infants.

PubMed

Oh, Ki Won; Koo, Mi Sung; Park, Hye Won; Chung, Mi Lim; Kim, Min-ho; Lim, Gina

2014-10-01

Thyroid dysfunction affects clinical complications in preterm infants and older children. However, thyroid hormone replacement in preterm infants has no proven benefits, possibly owing to the lack of an appropriate reference range for thyroid hormone levels. We aimed to establish a reference range for triiodothyronine (T3) levels at 1-month postnatal age (PNA) in preterm infants. This retrospective study included preterm infants born at a tertiary referral neonatal center at gestational age (GA)<35 weeks with no apparent thyroid dysfunction, for 6 consecutive years, with follow-up from PNA 2 weeks to 16 weeks. Using thyroid function tests (TFT), the relationships between T3 levels and thyrotropin (TSH) and free thyroxine (fT4) levels, birth weight, GA, postmenstrual age (PMA), and PNA were examined. The conversion trend for fT4 to T3 was analyzed using the T3/fT4 ratio. Overall, 464 TFTs from 266 infants were analyzed, after excluding 65 infants with thyroid dysfunction. T3 levels increased with fT4 levels, birth weight, GA, PMA, and PNA but not with TSH levels. The T3/fT4 ratio also increased with GA, PNA, and PMA. The average T3 level at 1 month PNA was 72.56 ± 27.83 ng/dL, with significant stratifications by GA. Relatively low T3 and fT4 levels in preterm infants were considered normal, with T3 levels and conversion trends increasing with GA, PMA, and PNA. Further studies are required to confirm the role of the present reference range in thyroid hormone replacement therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism

PubMed Central

KOBORI, HIROYUKI; ICHIHARA, ATSUHIRO; SUZUKI, HIROMICHI; TAKENAKA, TSUNEO; MIYASHITA, YUTAKA; HAYASHI, MATSUHIKO; SARUTA, TAKAO

2008-01-01

This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism. PMID:9277473

Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism.

PubMed

Kobori, H; Ichihara, A; Suzuki, H; Takenaka, T; Miyashita, Y; Hayashi, M; Saruta, T

1997-08-01

This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism.

Plasma Selenium Levels in First Trimester Pregnant Women with Hyperthyroidism and the Relationship with Thyroid Hormone Status.

PubMed

Arikan, Tugba Atilan

2015-10-01

The thyroid gland has the highest selenium (Se) concentration per unit weight among all tissues. The aims of the present study were to evaluate the Se levels in the plasma of hyperthyroidic pregnant women and to investigate the association between maternal plasma Se concentrations and thyroid hormone levels. The study population consisted of 107 pregnant women, 70 healthy pregnant women (group 1) and 37 pregnant women with hyperthyroidism (group 2). The plasma free triiodothyronine (fT3) and free thyroxine (fT4) levels were significantly higher, and the plasma thyroid-stimulating hormone (TSH) and Se levels were significantly lower in group 2 than in group 1 (p < 0.05). A correlation analysis showed a positive correlation between Se and fT4 in group 1 and with TSH in group 2 (p < 0.05). Decreased maternal serum antioxidant trace element Se in hyperthyroidic pregnant women compared with normal pregnant women supported the hypothesis that hyperthyroidism was associated with decreased antioxidant response.

Corticotropin-releasing hormone-mediated metamorphosis in the neotenic axolotl Ambystoma mexicanum: synergistic involvement of thyroxine and corticoids on brain type II deiodinase.

PubMed

Kühn, Eduard R; De Groef, Bert; Van der Geyten, Serge; Darras, Veerle M

2005-08-01

In the present study, morphological changes leading to complete metamorphosis have been induced in the neotenic axolotl Ambystoma mexicanum using a submetamorphic dose of T(4) together with an injection of corticotropin-releasing hormone (CRH). An injection of CRH alone is ineffective in this regard presumably due to a lack of thyrotropic stimulation. Using this low hormone profile for induction of metamorphosis, the deiodinating enzymes D2 and D3 known to be present in amphibians were measured in liver and brain 24h following an intraperitoneal injection. An injection of T(4) alone did not influence liver nor brain D2 and D3, but dexamethasone (DEX) or CRH alone or in combination with T(4) decreased liver D2 and D3. Brain D2 activity was slightly increased with a higher dose of DEX, though CRH did not have this effect. A profound synergistic effect occurred when T(4) and DEX or CRH were injected together, in the dose range leading to metamorphosis, increasing brain D2 activity more than fivefold. This synergistic effect was not found in the liver. It is concluded that brain T(3) availability may play an important role for the onset of metamorphosis in the neotenic axolotl.

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

Thickening of the epicardial adipose tissue can be alleviated by thyroid hormone replacement therapy in patients with subclinical hypothyroidism.

PubMed

Sayin, Irmak; Erkan, Aycan Fahri; Ekici, Berkay; Kutuk, Utku; Corakci, Ahmet; Tore, Hasan Fehmi

2016-01-01

Subclinical hypothyroidism (SCH) is a common disorder which has adverse cardiovascular effects. Epicardial adipose tissue (EAT), a novel marker of cardiovascular risk, is increased in SCH. We aimed to investigate whether L-thyroxine treatment can reverse the thickening of EAT in SCH. Forty-four patients with SCH and 42 euthyroid control subjects were included. EAT thickness was measured using transthoracic echocardiography at baseline and after restoration of the euthyroid status with 3 months of L-thyroxine treatment. At baseline, mean EAT thickness was significantly greater in the SCH group when compared to the control group (6.3 ± 1.7 mm vs. 4.1 ± 0.9 mm, respectively, p < 0.001). There was a significant positive correlation between baseline serum thyroid stimulating hormone (TSH) level and EAT thickness in the SCH group. There was a significant reduction in mean EAT thickness in response to L-thyroxine treatment (6.3 ± 1.7 mm vs. 5.1 ± 1.4 mm, p < 0.001). The decrease in EAT thickness after L-thyroxine treatment when compared to baseline (DEAT) significantly correlated to the difference in TSH levels before and after treatment (DTSH; r = 0.323; p = 0.032). Epicardial adipose tissue thickness is increased in patients with SCH. This thickening was alleviated with restoration of the euthyroid status with L-thyroxine treatment in our study population of predominantly male, relatively old subjects with greater baseline EAT thickness.

Waveguide Y-Circulator,

DTIC Science & Technology

1982-03-03

8217 AD-A112 086 FOREIGNl TECHNOL4OGY QIV WRIGHT-PATTERSON AFB OH F/6 9/1 WAVEB4JIDE Y -CIRCULATOR. 1W MAR 82 A A SH4IMKO, V N SHAKHGEOANOV UNCLASSIFIED...WAVEGUIDE Y -CIRCULATOR by A.A. Shimko, V.N. Shakhgedanov, et al °/ 1 tt, S N ,R 1 7 1982 :LE JApproved for public release; distribution unlimited. 82 03...csc csch csch arc csch csch-1 Russian English rot curl lg log , t ....... 0710 copy NS I,- j,’.D Waveguide Y -Circulator A. A. Shimko, V. N

Neuroendocrine recovery initiated by cognitive behavioral therapy in women with functional hypothalamic amenorrhea: a randomized controlled trial

PubMed Central

Michopoulos, Vasiliki; Mancini, Fulvia; Loucks, Tammy L.; Berga, Sarah L.

2013-01-01

Objective To determine whether cognitive behavior therapy (CBT), which we previously showed restored ovarian function in women with functional hypothalamic amenorrhea (FHA), also ameliorated hypercortisolemia and improved other neuroendocrine and metabolic concomitants of in FHA. Design Randomized controlled trial. Intervention CBT vs. observation. Setting Clinical research center at an academic medical university. Patient(s) Seventeen women with FHA were randomized either to CBT or observation. Main Outcome Measure(s) Circulatory concentrations of cortisol, leptin, TSH, total and free thyronine (T3), and total and free thyroxine (T4) before and immediately after completion of CBT or observation. Each woman served as her own control. Results CBT but not observation reduced cortisol levels in women with FHA. There were no changes in cortisol, leptin, TSH, T3, or T4 levels in women randomized to observation. Women treated with CBT showed increased levels of leptin and TSH, while levels of T3 and T4 remained unchanged. Conclusions CBT ameliorated hypercortisolism and improved neuroendocrine and metabolic concomitants of FHA while observation did not. We conclude that a cognitive, nonpharmacological approach aimed at alleviating problematic attitudes not only restored ovarian activity but also improved neuroendocrine and metabolic function in women with FHA. PMID:23507474

No significant effect of cannabis use on the count and percentage of circulating CD4 T-cells in HIV-HCV co-infected patients (ANRS CO13-HEPAVIH French cohort).

PubMed

Marcellin, Fabienne; Lions, Caroline; Rosenthal, Eric; Roux, Perrine; Sogni, Philippe; Wittkop, Linda; Protopopescu, Camelia; Spire, Bruno; Salmon-Ceron, Dominique; Dabis, François; Carrieri, Maria Patrizia

2017-03-01

Despite cannabis use being very common in patients co-infected with HIV and hepatitis C virus (HCV), its effect on these patients' immune systems remains undocumented. Documenting the potential effect of cannabis use on HIV immunological markers would help caregivers make more targeted health recommendations to co-infected patients. We performed a longitudinal analysis of the relationship between cannabis use and peripheral blood CD4 T-cell measures in co-infected patients receiving antiretroviral therapy. Cannabis use was assessed using annual self-administered questionnaires in 955 patients (2386 visits) enrolled in the ANRS CO13-HEPAVIH cohort. The effect of cannabis use on circulating CD4 T-cell count and percentage was estimated using multivariate linear regression models with generalised estimating equations. Sensitivity analyses were conducted after excluding visits where (i) tobacco use and (ii) smoking >=10 tobacco cigarettes/day were reported. At the first visit, 48% of patients reported cannabis use during the previous four weeks, and 58% of these patients also smoked ≥10 tobacco cigarettes/day. After multiple adjustment, cannabis use was not significantly associated with either circulating CD4 T-cell count [model coefficient (95% confidence interval): 0.27 (-0.07; 0.62), P = 0.12] or percentage [-0.04 (-0.45; 0.36), P = 0.83]. Sensitivity analyses confirmed these results. Findings show no evidence for a negative effect of cannabis use on circulating CD4 T-cell counts/percentages in HIV-HCV co-infected patients. In-depth immunological studies are needed to document whether cannabis has a harmful effect on CD4 levels in lungs and on cells' functional properties. [Marcellin F, Lions C, Rosenthal E, Roux P, Sogni P, Wittkop L, Protopopescu C, Spire B, Salmon-Ceron D, Dabis F, Carrieri MP, HEPAVIH ANRS CO13 Study Group. No significant effect of cannabis use on the count and percentage of circulating CD4 T-cells in HIV-HCV co-infected patients (ANRSCO13-HEPAVIH French cohort). Drug Alcohol Rev 2017;36:227-238]. © 2016 Australasian Professional Society on Alcohol and other Drugs.

Tissue-specific modulation of angiotensin-converting enzyme (ACE) in hyperthyroidism.

PubMed

Carneiro-Ramos, M S; Silva, V B; Santos, R A S; Barreto-Chaves, M L M

2006-11-01

We have previously demonstrated the interaction between the RAS and thyroid hormones (TH). The present study was designed to determine the role of TH in the local regulation of ACE activity and expression in different tissues. Adult male Wistar rats were randomized into three groups: T4-25 and T4-100 (0.025 and 0.100mg/kg of body weight/day of l-thyroxine for 14 days, respectively) and control. Hemodynamic parameters as well as cardiac and renal hypertrophy were evaluated. ACE activity and mRNA levels were determined by Fluorimetric and Northern blot assays, respectively. Both doses increased SBP and HR, as well as inducing cardiac and renal hypertrophy. Pulmonary and serum ACE levels were comparable among the groups. Both doses promoted increased renal ACE activity and expression but surprisingly ACE was diminished in the heart in both hyperthyroid groups. This change was mediated by a tissue-specific transcription mechanism.

Association between thyroid profile and perfluoroalkyl acids: Data from NHNAES 2007–2008

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

Jain, Ram B., E-mail: Jain.ram.b@gmail.com

The effect of six perfluoroalkyl acids (PFAAs), namely, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDE), perfluorohexane sulfonic acid (PFHxS), 2-(N-methyl-perfluorooctane sulfonamide) acetic acid (MPAH), and perfluorononanoic acid (PFNA) on the levels of six thyroid function variables, namely, thyroid stimulating hormone (TSH), free and total thyroxine (FT4, TT4), free and total triiodothyronine (FT3, TT3), and thyroglobulin (TGN) was evaluated. Data from National Health and Nutrition Examination Survey for the years 2007–2008 were used for this evaluation. TSH levels increased with increase in levels of PFOA (p<0.01). There were no statistically significant associations between the levels of FT3, and FT4more » with the levels of any of the six PFAAs. Levels of TT3 were found to increase with the levels of PFOA (p=0.01) and TT4 levels were found to increase with increase in PFHxS levels (p<0.01). Males had statistically significantly higher levels of FT3 than females and females had statistically significantly higher levels of TT4 than males. As compared to non-Hispanics whites and Hispanics, non-Hispanic blacks had lower levels of TSH, FT3, TT3, and TT4 but Hispanics had the lowest levels of TGN. Age was negatively associated with FT3 and TT3 but positively associated with FT4 and TT4. Non-smokers had higher levels of TSH and TT4 than smokers and smokers had higher levels of FT3 and TGN than non-smokers. Iodine deficiency was associated with increased levels of TSH, TT3, TT4, and TGN. -- Highlights: • Levels of total triiodothyronine were found to increase with the levels of PFOA. • Total thyroxine increased with increase in levels of perfluorohexane sulfonic acid. • There was a positive association between the levels of PFOA and TSH. • Iodine deficiency was associated with elevated levels of TSH, total T3 and T4. • Iodine deficiency was associated with elevated levels of thyroglobulin.« less

The role of 9-O-acetylated ganglioside D3 (CD60) and α4β1 (CD49d) expression in predicting the survival of patients with Sézary syndrome

PubMed Central

Scala, Enrico; Abeni, Damiano; Pomponi, Debora; Narducci, Maria Grazia; Lombardo, Giuseppe Alfonso; Mari, Adriano; Frontani, Marina; Picchio, Maria Cristina; Pilla, Maria Antonietta; Caprini, Elisabetta; Russo, Giandomenico

2010-01-01

Background Sézary syndrome is a rare and very aggressive leukemic variant of cutaneous T-cell lymphoma characterized by extensive skin involvement and a malignant circulating CD4+ T-cell clone which homes to the skin, over-expresses CD60, and lacks CD7, CD26 and CD49d. So far prognostic markers in this disease are limited to treatment with systemic steroids, age, serum lactate dehydrogenase, and a white blood cell count of 20×109/L or higher: no other biological marker with prognostic value, especially related to malignant cells, has been described. Design and Methods We used flow activated cell sorting analysis to compare the distribution of the T-cell receptor-Vβ repertoire and several surface molecules (CD7, CD26, CD49d and CD60) within the circulating CD4+ T-cell population in 62 patients with Sézary syndrome, 180 with mycosis fungoides, 6 with B-cell lymphomas, and 19 with chronic eczema. We calculated the 5-year overall survival of patients with Sézary syndrome after first hospital admission using Kaplan–Meier product–limit estimates and hazard ratios from the Cox proportional hazards model. Results We found that both higher number of CD60+ and lower number of CD49d+ cells within circulating CD4+ T cells at disease presentation were significantly associated with a lower probability of survival. An exceedingly high risk of death was observed for patients with a combination of a high proportion of CD4+CD60+ cells (≥ 0.5×109/L) and low proportion of CD4+CD49d+ cells (<0.5×109/L) (hazard ratio = 12.303, 95% confidence interval 1.5–95.9; P<0.02). In addition, a skewed usage of T-cell receptor-Vβ subfamilies was observed in the circulating T-cell clone for 61.9% of all patients with Sézary syndrome, T-cell receptor-Vβ 2 and 5.1 subfamilies being the most frequently represented (42.8%), followed by T-cell receptor-Vβ 12 and 13.1. Conclusions In this study we showed that up-regulation of CD60 and down-regulation of CD49d on circulating CD4+ T cells are two useful markers for predicting a very poor outcome in patients with Sézary syndrome. PMID:20663947

Total and free iodothyronine changes in response to transport of Equidae (Equus asinus and Equus caballus).

PubMed

Fazio, Esterina; Medica, Pietro; Cravana, Cristina; Ferlazzo, Adriana

2017-03-31

In this study the effects of short distance road transport on total and free iodothyronine changes in 12 stallions (Equus asinus and Equus caballus) were evaluated. Donkeys (n = 6) and horses (n = 6) were transported for a distance of 50 km. Blood samples were collected 1 week before transport in basal conditions, 1 week later immediately before loading, and after transport and unloading. After transport, donkeys showed significant increases in circulating T4 (P≤0.01), fT3 (P≤0.001), and fT4 (P≤0.01) levels; while horses had significant increases in circulating T3, fT3 and fT4 (P≤0.01) levels. Compared to donkeys' values, horses showed lower T4 values in basal condition, before and after transport (P≤0.001); higher fT3 values in basal condition and before (P≤0.001), and lower values (P≤0.001) after transport; higher fT4 values (P≤0.001) in basal condition. The results indicate that short road transport of donkeys and horses induces the activation of the thyroid gland, with the same release of fT3 and fT4 iodothyronines, but with different preferential release of T3 in horses and T4 in donkeys after transport.

Novel biomarkers of perchlorate exposure in zebrafish

USGS Publications Warehouse

Mukhi, S.; Carr, J.A.; Anderson, T.A.; Patino, R.

2005-01-01

Perchlorate inhibits iodide uptake by thyroid follicles and lowers thyroid hormone production. Although several effects of perchlorate on the thyroid system have been reported, the utility of these pathologies as markers of environmental perchlorate exposures has not been adequately assessed. The present study examined time-course and concentration-dependent effects of perchlorate on thyroid follicle hypertrophy, colloid depletion, and angiogenesis; alterations in whole-body thyroxine (T4) levels; and somatic growth and condition factor of subadult and adult zebrafish. Changes in the intensity of the colloidal T4 ring previously observed in zebrafish also were examined immunohistochemically. Three-month-old zebrafish were exposed to ammonium perchlorate at measured perchlorate concentrations of 0, 11, 90, 1,131, and 11,480 ppb for 12 weeks and allowed to recover in clean water for 12 weeks. At two weeks of exposure, the lowest-observed-effective concentrations (LOECs) of perchlorate that induced angiogenesis and depressed the intensity of colloidal T4 ring were 90 and 1,131 ppb, respectively; other parameters were not affected (whole-body T4 was not determined at this time). At 12 weeks of exposure, LOECs for colloid depletion, hypertrophy, angiogenesis, and colloidal T4 ring were 11,480, 1,131, 90, and 11 ppb, respectively. All changes were reversible, but residual effects on angiogenesis and colloidal T4 ring intensity were still present after 12 weeks of recovery (LOEC, 11,480 ppb). Whole-body T 4 concentration, body growth (length and weight), and condition factor were not affected by perchlorate. The sensitivity and longevity of changes in colloidal T4 ring intensity and angiogenesis suggest their usefulness as novel markers of perchlorate exposure. The 12-week LOEC for colloidal T4 ring is the lowest reported for any perchlorate biomarker in aquatic vertebrates. ?? 2005 SETAC.

Maternal thyroid dysfunction during gestation, preterm delivery, and birthweight. The Infancia y Medio Ambiente Cohort, Spain.

PubMed

León, Gemma; Murcia, Mario; Rebagliato, Marisa; Álvarez-Pedrerol, Mar; Castilla, Ane M; Basterrechea, Mikel; Iñiguez, Carmen; Fernández-Somoano, Ana; Blarduni, Elizabeth; Foradada, Carles M; Tardón, Adonina; Vioque, Jesús

2015-03-01

Maternal clinical thyroid disorders can cause reproductive complications. However, the effects of mild thyroid dysfunctions are not yet well established. The aim was to evaluate the association of maternal thyroid function during the first half of pregnancy with birthweight and preterm delivery. We analysed data on 2170 pregnant women and their children from a prospective population-based cohort study in four Spanish areas. Mid-gestation maternal serum and urine samples were gathered to determine thyroid-stimulating hormone (TSH), free thyroxine (fT4 ), and urinary iodine concentration (UIC). Thyroid status was defined according to percentile distribution as: euthyroid (TSH and fT4 >5th and <95th percentiles); hypothyroxinaemia (fT4  < 5 th percentile and TSH normal), hypothyroidism (TSH > 95th percentile and fT4 normal or <5th percentile), hyperthyroxinaemia (fT4  > 95 th percentile and TSH normal), and hyperthyroidism (TSH < 5 th percentile and fT4 normal or >95th percentile). Response variables were birthweight, small and large for gestational age (SGA/LGA), and preterm delivery. An inverse association of fT4 and TSH with birthweight was found, the former remaining when restricted to euthyroid women. High fT4 levels were also associated with an increased risk of SGA [odds ratio, 95% confidence interval (CI) 1.28 (95% CI 1.08, 1.51)]. Mean birthweight was higher in the hypothyroxinaemic group (β = 109, P < 0.01). Iodine intake and UIC were not associated with birth outcomes. High maternal fT4 levels during the first half of pregnancy were related to lower birthweight and increased risk of SGA newborns, suggesting that maternal thyroid function may affect fetal growth, even within the normal range. © 2015 John Wiley & Sons Ltd.

Colchicum autumnale in Patients with Goitre with Euthyroidism or Mild Hyperthyroidism: Indications for a Therapeutic Regulative Effect—Results of an Observational Study

PubMed Central

Scheffer, Christian; Debus, Marion; Heckmann, Christian; Cysarz, Dirk; Girke, Matthias

2016-01-01

Introduction. Goitre with euthyroid function or with subclinical or mild hyperthyroidism due to thyroid autonomy is common. In anthroposophic medicine various thyroid disorders are treated with Colchicum autumnale (CAU). We examined the effects of CAU in patients with goitre of both functional states. Patients and methods. In an observational study, 24 patients with goitre having suppressed thyroid stimulating hormone (TSH) levels with normal or slightly elevated free thyroxine (fT4) and free triiodothyronine (fT3) (group 1, n = 12) or normal TSH, fT3, and fT4 (group 2, n = 12) were included. After 3 months and after 6 to 12 months of CAU treatment, we investigated clinical pathology using the Hyperthyroid Symptom Scale (HSS), hormone status (TSH, fT4, and fT3), and thyroidal volume (tV). Results. After treatment with CAU, in group 1 the median HSS decreased from 4.5 (2.3–11.8) to 2 (1.3–3) (p < 0.01) and fT3 decreased from 3.85 (3.5–4.78) to 3.45 (3.3–3.78) pg/mL (p < 0.05). In group 2 tV (13.9% (18.5%–6.1%)) and TSH (p < 0.01) were reduced. Linear regression for TSH and fT3 in both groups indicated a regulative therapeutic effect of CAU. Conclusions. CAU positively changed the clinical pathology of subclinical hyperthyroidism and thyroidal volume in patients with euthyroid goitre by normalization of the regulation of thyroidal hormones. PMID:26955394

Colchicum autumnale in Patients with Goitre with Euthyroidism or Mild Hyperthyroidism: Indications for a Therapeutic Regulative Effect-Results of an Observational Study.

PubMed

Scheffer, Christian; Debus, Marion; Heckmann, Christian; Cysarz, Dirk; Girke, Matthias

2016-01-01

Introduction. Goitre with euthyroid function or with subclinical or mild hyperthyroidism due to thyroid autonomy is common. In anthroposophic medicine various thyroid disorders are treated with Colchicum autumnale (CAU). We examined the effects of CAU in patients with goitre of both functional states. Patients and methods. In an observational study, 24 patients with goitre having suppressed thyroid stimulating hormone (TSH) levels with normal or slightly elevated free thyroxine (fT4) and free triiodothyronine (fT3) (group 1, n = 12) or normal TSH, fT3, and fT4 (group 2, n = 12) were included. After 3 months and after 6 to 12 months of CAU treatment, we investigated clinical pathology using the Hyperthyroid Symptom Scale (HSS), hormone status (TSH, fT4, and fT3), and thyroidal volume (tV). Results. After treatment with CAU, in group 1 the median HSS decreased from 4.5 (2.3-11.8) to 2 (1.3-3) (p < 0.01) and fT3 decreased from 3.85 (3.5-4.78) to 3.45 (3.3-3.78) pg/mL (p < 0.05). In group 2 tV (13.9% (18.5%-6.1%)) and TSH (p < 0.01) were reduced. Linear regression for TSH and fT3 in both groups indicated a regulative therapeutic effect of CAU. Conclusions. CAU positively changed the clinical pathology of subclinical hyperthyroidism and thyroidal volume in patients with euthyroid goitre by normalization of the regulation of thyroidal hormones.

Is excessive weight gain after ablative treatment of hyperthyroidism due to inadequate thyroid hormone therapy?

PubMed

Tigas, S; Idiculla, J; Beckett, G; Toft, A

2000-12-01

There is controversy about the correct dose and form of thyroid hormone therapy for patients with hypothyroidism. Despite restoration of serum thyrotropin (TSH) concentrations to normal, many patients complain of excessive weight gain. We have compared weight at diagnosis of hyperthyroidism with that when euthyroid, evidenced by a stable, normal serum TSH concentration, with or without thyroxine (T4) replacement therapy, in patients treated with an 18-month course of antithyroid drugs (43 patients), surgery (56 patients), or 13I (34 patients) for Graves' disease. In addition, weights were recorded before and after treatment of 25 patients with differentiated thyroid carcinoma by total thyroidectomy, 131I, and long-term T4 suppressive therapy, resulting in undetectable serum TSH concentrations. Mean weight gain in patients with Graves' disease who required T4 replacement therapy following surgery was significantly greater than in those of the same age, sex, and severity of hyperthyroidism rendered euthyroid by surgery (3.9 kg) (p < 0.001) or at the end of a course of antithyroid drugs (4.1 kg) (p < 0.001). Weight gain was similar in those requiring T4 replacement following surgery or 131T therapy (10.4 versus 10.1 kg). In contrast, ablative therapy combined with suppression of TSH secretion by T4 in patients with differentiated thyroid carcinoma did not result in weight gain. The excessive weight gain in patients becoming hypothyroid after destructive therapy for Graves' disease suggests that restoration of serum TSH to the reference range by T4 alone may constitute inadequate hormone replacement.

Circulating magnesium levels and incidence of coronary heart diseases, hypertension, and type 2 diabetes mellitus: a meta-analysis of prospective cohort studies.

PubMed

Wu, Jiang; Xun, Pengcheng; Tang, Qingya; Cai, Wei; He, Ka

2017-09-19

Data on the associations between circulating magnesium (Mg) levels and incidence of coronary heart diseases (CHD), hypertension, and type 2 diabetes mellitus (T2DM) are inconsistent and inconclusive. The aim of this study was to examine circulating Mg levels in relation to incidence of CHD, hypertension, and T2DM. Prospective cohort studies published before May 2017 were searched through PubMed, EmBase, SCOPUS, and Google Scholar. A total of 11 studies that reported multivariable-adjusted associations of interest were identified. Information on the characteristics of study and participants, exposure, main outcomes, risk estimates, and cofounders was extracted and analyzed. Of the 11 included studies, 5 reported results on CHD (38,808 individuals [4437 cases] with an average 10.5-year follow-up), 3 on hypertension (14,876 participants [3149 cases] with a 6.7-year follow-up), and 4 on T2DM (31,284 participants [2680 cases] with an 8.8-year follow-up). Comparing the highest to the lowest category of circulating Mg concentration, the pooled relative risks [RRs] (95% confidence intervals [CIs]) were 0.86 (0.74, 0.996), 0.91 (0.80, 1.02), and 0.64 (0.50, 0.81) for incidence of CHD, hypertension, and T2DM, respectively. Every 0.1 mmol/L increment in circulating Mg levels was associated with 4% (RR, 0.96; 95% CI: 0.94, 0.99) reduction in hypertension incidence. No significant linear association was found between circulating Mg levels and incidence of CHD (RR, 0.89; 95% CI: 0.77, 1.03) and T2DM (RR, 0.90; 95% CI: 0.81, 1.002). The observed associations of interest were sensitive to exclusion of individual studies. Findings in this meta-analysis suggest that circulating Mg levels are inversely associated with incidence of CHD, hypertension, and T2DM. Additional studies are needed to provide more solid evidence and identify the optimal range of circulating Mg concentration with respect to primary prevention of CHD, hypertension, and T2DM.

Effects of experimentally induced maternal hypothyroidism and hyperthyroidism on the development of rat offspring: II-the developmental pattern of neurons in relation to oxidative stress and antioxidant defense system.

PubMed

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

2012-10-01

Excessive concentrations of free radicals in the developing brain may lead to neurons maldevelopment and neurons damage and death. Thyroid hormones (THs) states play an important role in affecting the modulation of oxidative stress and antioxidant defense system. Thus, the objective of this study was to clarify the effect of hypothyroidism and hyperthyroidism in rat dams on the neurons development of different brain regions of their offspring at several postnatal weeks in relation to changes in the oxidative stress and antioxidant defense system. The adult female rats were administered methimazole (MMI) in drinking water (0.02% w/v) from gestation day 1 to lactation day 21 to induce hypothyroidism and exogenous thyroxine (T4) in drinking water (0.002% w/v) beside intragastric incubation of 50--200 T4 μg/kg body weight (b. wt.) to induce hyperthyroidism. In normal female rats, the sera total thyroxine (TT4) and total triiodothyronine (TT3) levels were detectably increased at day 10 post-partum than those at day 10 of pregnancy. Free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH) and growth hormone (GH) concentrations in normal offspring were elevated at first, second and third postnatal weeks in an age-dependent manner. In hypothyroid group, a marked depression was observed in sera of dam TT3 and TT4 as well as offspring FT3, FT4 and GH, while there was a significant increase in TSH level with the age progress. The reverse pattern to latter state was recorded in hyperthyroid group. Concomitantly, in control offspring, the rate of neuron development in both cerebellar and cerebral cortex was increased in its density and complexity with age progress. This development may depend, largely, on THs state. Both maternal hypothyroidism and hyperthyroidism caused severe growth retardation in neurons of these regions of their offspring from the first to third weeks. Additionally, in normal offspring, seven antioxidant enzymes, four non-enzymatic antioxidants and one oxidative stress marker (lipid peroxidation, LPO) followed a synchronized course of alterations in cerebrum, cerebellum and medulla oblongata. In both thyroid states, the oxidative damage has been demonstrated by the increased LPO and inhibition of enzymatic and non-enzymatic antioxidants in most examined ages and brain regions. These disturbances in the antioxidant defense system led to deterioration in the neuronal maturation and development. In conclusion, it can be suggested that the maldevelopment of neurons and dendrites in different brain regions of offspring of hypothyroid and hyperthyroid mother rat dams may be attributed, at least in part, to the excess oxidative stress and deteriorated antioxidant defense system in such conditions. Published by Elsevier Ltd.

Study protocol; Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial (TRUST).

PubMed

Stott, David J; Gussekloo, Jacobijn; Kearney, Patricia M; Rodondi, Nicolas; Westendorp, Rudi G J; Mooijaart, Simon; Kean, Sharon; Quinn, Terence J; Sattar, Naveed; Hendry, Kirsty; Du Puy, Robert; Den Elzen, Wendy P J; Poortvliet, Rosalinde K E; Smit, Jan W A; Jukema, J Wouter; Dekkers, Olaf M; Blum, Manuel; Collet, Tinh-Hai; McCarthy, Vera; Hurley, Caroline; Byrne, Stephen; Browne, John; Watt, Torquil; Bauer, Douglas; Ford, Ian

2017-02-03

Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH. Participants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects <50Kg body weight or known coronary heart disease) with titration of dose in the active treatment group according to TSH level, and a mock titration in the placebo group. The primary outcomes are changes in two domains (hypothyroid symptoms and fatigue / vitality) on the thyroid-related quality of life questionnaire (ThyPRO) at one year. The study has 80% power (at p = 0.025, 2-tailed) to detect a change with levothyroxine treatment of 3.0% on the hypothyroid scale and 4.1% on the fatigue / vitality scale with a total target sample size of 750 patients. Secondary outcomes include general health-related quality of life (EuroQol), fatal and non-fatal cardiovascular events, handgrip strength, executive cognitive function (Letter Digit Coding Test), basic and instrumental activities of daily living, haemoglobin, blood pressure, weight, body mass index and waist circumference. Patients are monitored for specific adverse events of interest including incident atrial fibrillation, heart failure and bone fracture. This large multicentre RCT of levothyroxine treatment of subclinical hypothyroidism is powered to detect clinically relevant change in symptoms / quality of life and is likely to be highly influential in guiding treatment of this common condition. Clinicaltrials.gov NCT01660126 ; registered 8th June 2012.

CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells are positively correlated with levels of IL-21 in active and transitional cystic echinococcosis patients.

PubMed

Zhang, Fengbo; Pang, Nannan; Zhu, Yuejie; Zhou, Dexian; Zhao, Hui; Hu, Jinwei; Ma, Xiumin; Li, Jun; Wen, Hao; Samten, Buka; Fan, Haining; Ding, Jianbing

2015-10-26

In our study, we investigated whether circulating T follicular helper (Tfh) and the related cytokines are involved in human cystic echinococcosis (CE). A total of 64 patients with CE and 30 healthy controls were enrolled in this study. Percentages of CCR7(lo)PD-1(hi) cells within CXCR5(+) CD4(+) T cells (circulating Tfh cells) were detected by flow cytometry. Levels of IL-21 and IL-4 in peripheral blood were detected by cytometric bead array. The mRNA expression of IL-21, IL-4, Bcl-6, and Blimp-1 in peripheral blood mononuclear cells (PBMCs) were measured by real-time PCR. Levels of IgG1, IgG2, IgG3, and IgG4 in the patients' sera were measured using enzyme-linked immunosorbent assay. Percentages of circulating Tfh cells were significantly increased in the CE1, CE2, and CE3 groups (p < 0.05). The concentrations of IL-21 and IL-4 in the serum were significantly increased in CE1, CE2, and CE3 groups (p < 0.05). IL-21 was positively correlated with circulating Tfh cells in CE3 group (r = 0.779, p < 0.05). The mRNA levels of IL-21, IL-4, and Bcl-6 were increased in CE1, CE2, and CE3 groups. Levels of IgG1 and IgG4 in patients' sera were increased in CE1, CE2, and CE3 groups. Levels of IgG2 and IgG3 were increased in CE4-5 group. Additionally, after stimulation with hydatid fluid in vitro, the levels of circulating Tfh cells, IL-21 and IL-4 in PBMCs isolated from CE patients were significantly increased (p < 0.05). The levels of circulating Tfh and related cytokines were significantly increased in CE patients, suggesting that they are involved in human CE.

Comparison of conventional L-thyroxine withdrawal and moderate hypothyroidism in preparation for whole-body 131-I scan and thyroglobulin testing.

PubMed

Marturano, I; Russo, M; Spadaro, A; Latina, A; Malandrino, P; Regalbuto, C

2015-09-01

After thyroidectomy for thyroid cancer, patients often withdraw L-T4 for diagnostic or therapeutic purposes, showing signs and symptoms of hypothyroidism. A slighter hypothyroidism (reducing L-T4 to one-half) has been proposed to limit these inconveniences. We evaluated half-dose L-T4 protocol, in comparison to conventional L-T4 withdrawal, in terms of effectiveness and improvement of clinical and biochemical disorders. We randomized 55 thyroid cancer patients into two groups: 29 patients underwent 5 weeks of half-dose of previous L-T4 treatment (HD group); 26 patients replaced L-T4 with L-T3 for 3 weeks followed by 2 weeks of withdrawal (TW group). Clinical features (Zulewsky clinical score) and biochemical parameters (lipids, liver, and muscle enzymes) were evaluated in all patients at baseline and after 5 weeks. Total cholesterol, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase increased at 5 weeks in both groups, but significantly more in TW, but no difference was found by clinical score. Patients who achieved the thyroid-stimulating hormone (TSH) target value (25 µU/ml) were 92.3% in TW group and 48.3% in HD group (p < 0.001). In the HD group, only basal TSH statistically correlated with the achievement of the TSH target. Receiver operating characteristic curves indicated that a basal TSH ≥0.52 μU/ml is required to reach an adequate TSH level. Half-dose L-T4 protocol, compared to conventional L-T4 withdrawal, is associated with less biochemical disorders but no significant clinical advantage. Therefore, the half-dose protocol reaches an adequate TSH target in 48.3% of patients and is not effective unless basal serum TSH is ≥0.52 μU/ml.

The role of AT1-receptor blockade on reactive oxygen species and cardiac autonomic drive in experimental hyperthyroidism.

PubMed

Baraldi, D; Casali, K; Fernandes, R O; Campos, C; Sartório, C; Conzatti, A; Couto, G K; Schenkel, P C; Belló-Klein, A; Araujo, A R S

2013-10-01

The objective of this study was to explore the influence of the renin-angiotensin system on cardiac prooxidants and antioxidants levels and its association to autonomic imbalance induced by hyperthyroidism. Male Wistar rats were divided into four groups: control, losartan (10mg/kg/day by gavage, 28 day), thyroxine (T4) (12 mg/L in drinking water for 28 days), and T4+losartan. Spectral analysis (autonomic balance), angiotensin II receptor (AT1R), NADPH oxidase, Nrf2 and heme-oxygenase-1 (HO-1) myocardial protein expression, and hydrogen peroxide (H2O2) concentration were quantified. Autonomic imbalance induced by hyperthyroidism (~770%) was attenuated in the T4+losartan group (~32%) (P<0.05). AT1R, NADPH oxidase, H2O2, as well as concentration, Nrf2 and HO-1 protein expression were elevated (~172%, 43%, 40%, 133%, and 154%, respectively) in T4 group (P<0.05). H2O2 and HO-1 levels were returned to control values in the T4+losartan group (P<0.05). The overall results demonstrate a positive impact of RAS blockade in the autonomic control of heart rate, which was associated with an attenuation of H2O2 levels, as well as with a reduced counter-regulatory response of HO-1 in experimental hyperthyroidism. Copyright © 2013 Elsevier B.V. All rights reserved.

Thyroid stimulation with recombinant human thyrotropin in healthy cats, cats with non-thyroidal illness and in cats with low serum thyroxin and azotaemia after treatment of hyperthyroidism.

PubMed

van Hoek, Ingrid M; Vandermeulen, Eva; Peremans, Kathelijne; Daminet, Sylvie

2010-02-01

This study investigated the recombinant human thyrotropin (rhTSH) stimulation test in healthy cats (group 1), cats with non-thyroidal illness (group 2) and cats with low serum total T(4) (TT(4)) and azotaemia after (131)I treatment (group 3). Serum TT(4) responses and thyroidal pertechnetate uptake after administration of 25 microg rhTSH IV were assessed. Baseline serum TT(4) was significantly lower in group 3 compared with group 1, but not between other group pairs. Serum TT(4) increased significantly in groups 1 and 2 but not in group 3 after rhTSH administration. Post-rhTSH serum TT(4) concentrations differed significantly between groups 1 and 3 and groups 2 and 3, but not between groups 1 and 2. Thyroid/salivary gland uptake ratio (T/S uptake ratio) differed only significantly between groups 1 and 3. Stimulation with rhTSH is valuable to differentiate euthyroidism from iatrogenic hypothyroidism in cats. Copyright 2009 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Analysis of current thyroid function test ordering practices.

PubMed

Kluesner, Joseph K; Beckman, Darrick J; Tate, Joshua M; Beauvais, Alexis A; Kravchenko, Maria I; Wardian, Jana L; Graybill, Sky D; Colburn, Jeffrey A; Folaron, Irene; True, Mark W

2018-04-01

Current guidelines recommend thyroid stimulating hormone (TSH) alone as the best test to detect and monitor thyroid dysfunction, yet free thyroxine (FT4) and free triiodothyronine (FT3) are commonly ordered when not clinically indicated. Excessive testing can lead to added economic burden in an era of rising healthcare costs, while rarely contributing to the evaluation or management of thyroid disease. To evaluate our institution's practice in ordering thyroid function tests (TFTs) and to identify strategies to reduce inappropriate FT4 and FT3 testing. A record of all TFTs obtained in the San Antonio Military Health System during a 3-month period was extracted from the electronic medical record. The TFTs of interest were TSH, FT4, thyroid panel (TSH + FT4), FT3, total thyroxine (T4), and total triiodothyronine (T3). These were categorized based on the presence or absence of hypothyroidism. Between August 1 and October 31, 2016, there were 38 214 individual TFTs ordered via 28 597 total laboratory requests; 11 486 of these requests were in patients with a history of hypothyroidism. The number (percent) of laboratory requests fell into these patterns: TSH alone 14 919 (52.14%), TSH + FT4 7641 (26.72%), FT3 alone 3039 (10.63%), FT4 alone 1219 (4.26%), TSH + FT4 + FT3 783 (2.74%), and others 996 (3.48%); 36.0% of TFTs ordered were free thyroid hormones. Projected out to a year, using Department of Defense laboratory costs, $317 429 worth of TFTs would be ordered, with free thyroid hormone testing accounting for $107 720. Inappropriate ordering of free thyroid hormone tests is common. In an era of rising healthcare costs, inappropriate thyroid function testing is an ideal target for efforts to reduce laboratory overutilization, which in our system, could save up to $120 000 per year. Further evaluation is needed to determine strategies that can reduce excessive thyroid hormone testing. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Dual role of betel leaf extract on thyroid function in male mice.

PubMed

Panda, S; Kar, A

1998-12-01

The effects of betel leaf extract (0.10, 0.40, 0.80 and 2.0 g kg-1 day-1 for 15 days) on the alterations in thyroid hormone concentrations. lipid peroxidation (LPO) and on the activities of superoxide dismutase (SOD) and catalase (CAT) were investigated in male Swiss mice. Administration of betel leaf extract exhibited a dual role, depending on the different doses. While the lowest dose decreased thyroxine (T4) and increased serum triiodothyronine (T3) concentrations, reverse effects were observed at two higher doses. Higher doses also increased LPO with a concomitant decrease in SOD and CAT activities. However, with the lowest dose most of these effects were reversed. These findings suggest that betel leaf can be both stimulatory and inhibitory to thyroid function, particularly for T3 generation and lipid peroxidation in male mice, depending on the amount consumed.

Lower numbers of circulating natural killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease

PubMed Central

Ndhlovu, L C; Snyder-Cappione, J E; Carvalho, K I; Leal, F E; Loo, C P; bruno, F R; Jha, A R; Devita, D; Hasenkrug, A M; Barbosa, H M R; Segurado, A C; Nixon, D F; Murphy, E L; Kallas, E G

2009-01-01

Human T lymphotropic virus type 1 (HTLV-1) infects 10–20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: São Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4+ and fewer CD8+ cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4+ NK T subset are associated with HTLV-1 disease progression. PMID:19778295

Induction of the UDP-Glucuronosyltransferase 1A1 during the Perinatal Period Can Cause Neurodevelopmental Toxicity.

PubMed

Hirashima, Rika; Michimae, Hirofumi; Takemoto, Hiroaki; Sasaki, Aya; Kobayashi, Yoshinori; Itoh, Tomoo; Tukey, Robert H; Fujiwara, Ryoichi

2016-09-01

Anticonvulsants can increase the risk of developing neurotoxicity in infants; however, the underlying mechanism has not been elucidated to date. Thyroxine [3,5,3',5'-l-tetraiodothyronine (T4)] plays crucial roles in the development of the central nervous system. In this study, we hypothesized that induction of UDP-glucuronosyltransferase 1A1 (UGT1A1)-an enzyme involved in the metabolism of T4-by anticonvulsants would reduce serum T4 levels and cause neurodevelopmental toxicity. Exposure of mice to phenytoin during both the prenatal and postnatal periods significantly induced UGT1A1 and decreased serum T4 levels on postnatal day 14. In the phenytoin-treated mice, the mRNA levels of synaptophysin and synapsin I in the hippocampus were lower than those in the control mice. The thickness of the external granule cell layer was greater in phenytoin-treated mice, indicating that induction of UGT1A1 during the perinatal period caused neurodevelopmental disorders. Exposure to phenytoin during only the postnatal period also caused these neurodevelopmental disorders. A T4 replacement attenuated the increase in thickness of the external granule cell layer, indicating that the reduced T4 was specifically associated with the phenytoin-induced neurodevelopmental disorder. In addition, these neurodevelopmental disorders were also found in the carbamazepine- and pregnenolone-16-α-carbonitrile-treated mice. Our study is the first to indicate that UGT1A1 can control neurodevelopment by regulating serum T4 levels. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Induction of the UDP-Glucuronosyltransferase 1A1 during the Perinatal Period Can Cause Neurodevelopmental Toxicity

PubMed Central

Hirashima, Rika; Michimae, Hirofumi; Takemoto, Hiroaki; Sasaki, Aya; Kobayashi, Yoshinori; Itoh, Tomoo; Tukey, Robert H.

2016-01-01

Anticonvulsants can increase the risk of developing neurotoxicity in infants; however, the underlying mechanism has not been elucidated to date. Thyroxine [3,5,3′,5′-l-tetraiodothyronine (T4)] plays crucial roles in the development of the central nervous system. In this study, we hypothesized that induction of UDP-glucuronosyltransferase 1A1 (UGT1A1)—an enzyme involved in the metabolism of T4—by anticonvulsants would reduce serum T4 levels and cause neurodevelopmental toxicity. Exposure of mice to phenytoin during both the prenatal and postnatal periods significantly induced UGT1A1 and decreased serum T4 levels on postnatal day 14. In the phenytoin-treated mice, the mRNA levels of synaptophysin and synapsin I in the hippocampus were lower than those in the control mice. The thickness of the external granule cell layer was greater in phenytoin-treated mice, indicating that induction of UGT1A1 during the perinatal period caused neurodevelopmental disorders. Exposure to phenytoin during only the postnatal period also caused these neurodevelopmental disorders. A T4 replacement attenuated the increase in thickness of the external granule cell layer, indicating that the reduced T4 was specifically associated with the phenytoin-induced neurodevelopmental disorder. In addition, these neurodevelopmental disorders were also found in the carbamazepine- and pregnenolone-16-α-carbonitrile–treated mice. Our study is the first to indicate that UGT1A1 can control neurodevelopment by regulating serum T4 levels. PMID:27413119

RhoA/ROCK may involve in cardiac hypertrophy induced by experimental hyperthyroidism.

PubMed

Na, Wang; Peng, Guan; Jianping, Zhang; Yanzhong, Chang; Shengjiang, Guan; Li, Chu

2012-10-01

In this study, the role of the RhoA/Rho-kinase (RhoA/ROCK)-signaling pathway in cardiovascular dysfunction associated with hyperthyroidism was examined with the use of fasudil, a Rho-kinase inhibitor. Male Spraque-Dawley rats were treated with l-thyroxine (T(4)) alone, T(4) + low-dose fasudil (2 mg/kg/day) or T(4) + high-dose fasudil (10 mg/kg/day) and compared with control animals. Rats in the T(4) group showed an increase in the ratio of heart weight to body weight, which was ameliorated by fasudil at both low and high doses. Morphometric and hemodynamic parameters were also evaluated and confirmed that fasudil attenuated the cardiac hypertrophy induced by T(4). The extent of phosphorylation of the myosin phosphatase targeting subunit was quantified by Western blotting to evaluate the activity of Rho-kinase in the heart tissue. Both Western blotting and reverse transcriptase-polymerase chain reaction analyses revealed enhancement of Rho-kinase and activator protein 1 activity and reduction of c-FLIP(L) expression in the T(4) group, and this response was inhibited by fasudil in a dose-dependent manner. Furthermore, fasudil inhibited apoptosis induced by T(4) as evidenced by the detection of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and the expressions of bax and bcl-2. These results suggested that the RhoA/ROCK pathway is involved in the cardiac hypertrophy induced by experimental hyperthyroidism. The antagonism of this pathway may thus be useful as an alternative target in the treatment of hyperthyroid heart disease.

Systematic appraisal of lactose intolerance as cause of increased need for oral thyroxine.

PubMed

Cellini, Miriam; Santaguida, Maria Giulia; Gatto, Ilenia; Virili, Camilla; Del Duca, Susanna Carlotta; Brusca, Nunzia; Capriello, Silvia; Gargano, Lucilla; Centanni, Marco

2014-08-01

An increased need for T4 has been described in patients with different gastrointestinal disorders. However, there is a lack of systematic studies assessing the need for T4 in hypothyroid patients with lactose intolerance, a widespread and often occult disorder. The objective of the study was to assess the replacement T4 dose required in hypothyroid patients with lactose intolerance. This was a cohort study. The study was conducted at an outpatient endocrinology unit in a University Hospital. The replacement T4 dose has been analyzed, from 2009 to 2012, in 34 hypothyroid patients due to Hashimoto's thyroiditis and lactose intolerance and being noncompliant with a lactose-free diet. An individually tailored T4 dose was measured. In all patients with isolated Hashimoto's thyroiditis, target TSH (median TSH 1.02 mU/L) was obtained at a median T4 dose of 1.31 μg/kg/d. In patients with lactose intolerance, only five of 34 patients reached the desired TSH (median TSH 0.83 mU/L) with a similar T4 dose (1.29 μg/kg/d). In the remaining 29 patients, the T4 dose was progressively increased and the target TSH (median TSH 1.21 mU/L) was attained at a median T4 dose of 1.81 μg/kg/d (+38%, P < .0001). In six of these patients, other gastrointestinal disorders were diagnosed, and their median T4 requirement was higher (2.04 μg/kg/d; +55%; P = .0032). In the remaining 23 patients with isolated lactose intolerance, a median T4 dose of 1.72 μg/kg/d (+31% P < .0001) has been required to attain pharmacological thyroid homeostasis. These findings show that lactose intolerance significantly increased the need for oral T4 in hypothyroid patients.

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.

Hepatic amino nitrogen conversion and organ N-contents in hypothyroidism, with thyroxine replacement, and in hyperthyroid rats.

PubMed

Grøfte, T; Wolthers, T; Jensen, D S; Møller, N; Jørgensen, J O; Orskov, H; Vilstrup, H

1997-02-01

The role of thyroid hormones in the regulation of hepatic conversions of amino nitrogen to urea is unresolved. The present study was designed to assess ureagenesis in rats with experimentally well-established hypo- and hyperthyroidism. The possible role of propylthiuracil (PTU), used for induction of hypothyroidism, was ascertained during thyroxine replacement of PTU treated hypothyroid rats. Basal blood amino nitrogen concentrations (AAN), the urea nitrogen synthesis rate (UNSR) and the maximal hepatic capacity for urea nitrogen synthesis (CUNS) obtained during alanine infusion were determined together with N-contents in the soleus muscle and kidneys in experimentally hypothyroid rats (n = 19), upon thyroxine replacement (n = 14) and in experimentally hyperthyroid rats (n = 19). Hypothyroidism was induced by adding propylthiouracil (0.05%) to the drinking water for 5 weeks. Hyperthyroidism was induced by thyroxine 100 micrograms/100 g body weight. During hyperthyroidism, T3 fell to less than 10%, food intake was halved, and body weight fell by 13%. Basal blood AAN fell by 25% (p < 0.01), UNSR more than doubled (p < 0.01), and CUNS rose by 45% (p < 0.05). N-contents of the soleus muscle fell by 13% and by 20% in kidneys, respectively (p < 0.05). Thyroxine replacement normalized AAN, UNSR, CUNS and reduced N-loss to 7% in the soleus muscle (NS) and kidneys (p < 0.05), respectively. During hyperthyroidism, T3 rose five-fold, food intake rose by two thirds, and body weight fell by 10%. Basal AAN rose by 20% (p < 0.05), UNSR doubled (p < 0.01), and CUNS rose by 25% (p < 0.05). N-contents of the soleus muscle decreased by 19%, whereas kidney N-contents increased by 25% (p < 0.05). Overall liver function assessed by galactose elimination capacity did not differ among groups. Both conditions increased the rate of urea synthesis; in the hypothyroid state the hepatic waste of amino-N was limited by low blood concentration of amino-N, probably due to lower proteolysis. In the hyperthyroid state hepatic amino-N loss was aggravated by higher blood concentration of amino-N, probably due to higher proteolysis. This difference may explain the markedly different dietary nitrogen economy between the two groups. The findings suggest that distinct hepatic acceleration of urea synthesis may contribute to the protein loss seen in both myxedema and in thyrotoxicosis in humans.

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

PubMed

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

2018-01-01

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

Thyroid Hormone in the Clinic and Breast Cancer.

PubMed

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

2018-06-01

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

Blocking the recruitment of naive CD4+ T cells reverses immunosuppression in breast cancer

PubMed Central

Su, Shicheng; Liao, Jianyou; Liu, Jiang; Huang, Di; He, Chonghua; Chen, Fei; Yang, LinBing; Wu, Wei; Chen, Jianing; Lin, Ling; Zeng, Yunjie; Ouyang, Nengtai; Cui, Xiuying; Yao, Herui; Su, Fengxi; Huang, Jian-dong; Lieberman, Judy; Liu, Qiang; Song, Erwei

2017-01-01

The origin of tumor-infiltrating Tregs, critical mediators of tumor immunosuppression, is unclear. Here, we show that tumor-infiltrating naive CD4+ T cells and Tregs in human breast cancer have overlapping TCR repertoires, while hardly overlap with circulating Tregs, suggesting that intratumoral Tregs mainly develop from naive T cells in situ rather than from recruited Tregs. Furthermore, the abundance of naive CD4+ T cells and Tregs is closely correlated, both indicating poor prognosis for breast cancer patients. Naive CD4+ T cells adhere to tumor slices in proportion to the abundance of CCL18-producing macrophages. Moreover, adoptively transferred human naive CD4+ T cells infiltrate human breast cancer orthotopic xenografts in a CCL18-dependent manner. In human breast cancer xenografts in humanized mice, blocking the recruitment of naive CD4+ T cells into tumor by knocking down the expression of PITPNM3, a CCL18 receptor, significantly reduces intratumoral Tregs and inhibits tumor progression. These findings suggest that breast tumor-infiltrating Tregs arise from chemotaxis of circulating naive CD4+ T cells that differentiate into Tregs in situ. Inhibiting naive CD4+ T cell recruitment into tumors by interfering with PITPNM3 recognition of CCL18 may be an attractive strategy for anticancer immunotherapy. PMID:28290464

Effect of thyroid hormone concentration on the transcriptional response underlying induced metamorphosis in the Mexican axolotl (Ambystoma)

PubMed Central

Page, Robert B; Voss, Stephen R; Samuels, Amy K; Smith, Jeramiah J; Putta, Srikrishna; Beachy, Christopher K

2008-01-01

Background Thyroid hormones (TH) induce gene expression programs that orchestrate amphibian metamorphosis. In contrast to anurans, many salamanders do not undergo metamorphosis in nature. However, they can be induced to undergo metamorphosis via exposure to thyroxine (T4). We induced metamorphosis in juvenile Mexican axolotls (Ambystoma mexicanum) using 5 and 50 nM T4, collected epidermal tissue from the head at four time points (Days 0, 2, 12, 28), and used microarray analysis to quantify mRNA abundances. Results Individuals reared in the higher T4 concentration initiated morphological and transcriptional changes earlier and completed metamorphosis by Day 28. In contrast, initiation of metamorphosis was delayed in the lower T4 concentration and none of the individuals completed metamorphosis by Day 28. We identified 402 genes that were statistically differentially expressed by ≥ two-fold between T4 treatments at one or more non-Day 0 sampling times. To complement this analysis, we used linear and quadratic regression to identify 542 and 709 genes that were differentially expressed by ≥ two-fold in the 5 and 50 nM T4 treatments, respectively. Conclusion We found that T4 concentration affected the timing of gene expression and the shape of temporal gene expression profiles. However, essentially all of the identified genes were similarly affected by 5 and 50 nM T4. We discuss genes and biological processes that appear to be common to salamander and anuran metamorphosis, and also highlight clear transcriptional differences. Our results show that gene expression in axolotls is diverse and precise, and that axolotls provide new insights about amphibian metamorphosis. PMID:18267027

Effect of thyroid hormone concentration on the transcriptional response underlying induced metamorphosis in the Mexican axolotl (Ambystoma).

PubMed

Page, Robert B; Voss, Stephen R; Samuels, Amy K; Smith, Jeramiah J; Putta, Srikrishna; Beachy, Christopher K

2008-02-11

Thyroid hormones (TH) induce gene expression programs that orchestrate amphibian metamorphosis. In contrast to anurans, many salamanders do not undergo metamorphosis in nature. However, they can be induced to undergo metamorphosis via exposure to thyroxine (T4). We induced metamorphosis in juvenile Mexican axolotls (Ambystoma mexicanum) using 5 and 50 nM T4, collected epidermal tissue from the head at four time points (Days 0, 2, 12, 28), and used microarray analysis to quantify mRNA abundances. Individuals reared in the higher T4 concentration initiated morphological and transcriptional changes earlier and completed metamorphosis by Day 28. In contrast, initiation of metamorphosis was delayed in the lower T4 concentration and none of the individuals completed metamorphosis by Day 28. We identified 402 genes that were statistically differentially expressed by > or = two-fold between T4 treatments at one or more non-Day 0 sampling times. To complement this analysis, we used linear and quadratic regression to identify 542 and 709 genes that were differentially expressed by > or = two-fold in the 5 and 50 nM T4 treatments, respectively. We found that T4 concentration affected the timing of gene expression and the shape of temporal gene expression profiles. However, essentially all of the identified genes were similarly affected by 5 and 50 nM T4. We discuss genes and biological processes that appear to be common to salamander and anuran metamorphosis, and also highlight clear transcriptional differences. Our results show that gene expression in axolotls is diverse and precise, and that axolotls provide new insights about amphibian metamorphosis.

Effect of UGT1A1, UGT1A3, DIO1 and DIO2 polymorphisms on L-thyroxine doses required for TSH suppression in patients with differentiated thyroid cancer.

PubMed

Santoro, Ana B; Vargens, Daniela D; Barros Filho, Mateus de Camargo; Bulzico, Daniel A; Kowalski, Luiz Paulo; Meirelles, Ricardo M R; Paula, Daniela P; Neves, Ronaldo R S; Pessoa, Cencita N; Struchine, Claudio J; Suarez-Kurtz, Guilherme

2014-11-01

To evaluate the impact of genetic polymorphisms in uridine 5'-glucuronosylytansferases UGT1A1 and UGT1A3 and iodothyronine-deiodinases types 1 and 2 on levothyroxine (T4 ; 3,5,3',5'-triiodo-L-thyronine) dose requirement for suppression of thyrotropin (TSH) secretion in patients with differentiated thyroid cancer (DTC). Patients (n = 268) submitted to total thyroidectomy and ablation by (131) I, under T4 therapy for at least 6 months were recruited in three public institutions in Brazil. Multivariate regression modelling was applied to assess the association of T4 dosing with polymorphisms in UGT1A1 (rs8175347), UGT1A3 (rs3806596 and rs1983023), DIO1 (rs11206244 and rs2235544) and DIO2 (rs225014 and rs12885300), demographic and clinical variables. A regression model including UGT1A haplotypes, age, gender, body weight and serum TSH concentration accounted for 39% of the inter-individual variation in the T4 dosage. The association of T4 dose with UGT1A haplotype is attributed to reduced UGT1A1 expression and T4 glucuronidation in liver of carriers of low expression UGT1A1 rs8175347 alleles. The DIO1 and DIO2 genotypes had no influence of T4 dosage. UGT1A haplotypes associate with T4 dosage in DTC patients, but the effect accounts for only 2% of the total variability and recommendation of pre-emptive UGT1A genotyping is not warranted. © 2014 The British Pharmacological Society.

Effect of UGT1A1, UGT1A3, DIO1 and DIO2 polymorphisms on L-thyroxine doses required for TSH suppression in patients with differentiated thyroid cancer

PubMed Central

Santoro, Ana B; Vargens, Daniela D; Barros Filho, Mateus de Camargo; Bulzico, Daniel A; Kowalski, Luiz Paulo; Meirelles, Ricardo M R; Paula, Daniela P; Neves, Ronaldo R S; Pessoa, Cencita N; Struchine, Claudio J; Suarez-Kurtz, Guilherme

2014-01-01

Aim To evaluate the impact of genetic polymorphisms in uridine 5′-glucuronosylytansferases UGT1A1 and UGT1A3 and iodothyronine-deiodinases types 1 and 2 on levothyroxine (T4; 3,5,3′,5′-triiodo-L-thyronine) dose requirement for suppression of thyrotropin (TSH) secretion in patients with differentiated thyroid cancer (DTC). Methods Patients (n = 268) submitted to total thyroidectomy and ablation by 131I, under T4 therapy for at least 6 months were recruited in three public institutions in Brazil. Multivariate regression modelling was applied to assess the association of T4 dosing with polymorphisms in UGT1A1 (rs8175347), UGT1A3 (rs3806596 and rs1983023), DIO1 (rs11206244 and rs2235544) and DIO2 (rs225014 and rs12885300), demographic and clinical variables. Results A regression model including UGT1A haplotypes, age, gender, body weight and serum TSH concentration accounted for 39% of the inter-individual variation in the T4 dosage. The association of T4 dose with UGT1A haplotype is attributed to reduced UGT1A1 expression and T4 glucuronidation in liver of carriers of low expression UGT1A1 rs8175347 alleles. The DIO1 and DIO2 genotypes had no influence of T4 dosage. Conclusion UGT1A haplotypes associate with T4 dosage in DTC patients, but the effect accounts for only 2% of the total variability and recommendation of pre-emptive UGT1A genotyping is not warranted. PMID:24910925

Cardiac and renal antioxidant enzymes and effects of tempol in hyperthyroid rats.

PubMed

Moreno, Juan Manuel; Rodríguez Gómez, Isabel; Wangensteen, Rosemary; Osuna, Antonio; Bueno, Pablo; Vargas, Félix

2005-11-01

This study evaluated the activity of cardiac and renal antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR)] and whether chronic treatment with tempol, a cell membrane-permeable SOD mimetic, ameliorates the hypertension of hyperthyroidism. Two experiments were performed. In experiment I, the following four groups of male Wistar rats were used: control group and three groups that received thyroxine (T4) at 10, 50, or 75 microg x rat(-1) x day(-1). In experiment II, tempol was orally administered (18 mg x kg(-1) x day(-1)) to control and T4-treated (75 microg x rat(-1) x day(-1)) rats. All treatments were maintained for 6 wk. Body weight, tail systolic blood pressure (BP), and heart rate were measured one time a week, and direct BP and morphological, metabolic, plasma, and renal variables were measured at the end of the experiment. Enzymatic activities were measured in renal cortex and medulla and right and left ventricles. In renal cortex, SOD activity was decreased in the T4-75 group, and there was a dose-related increase in CAT activity and decrease in GPX and GR activities in T4-treated groups. Activity of all antioxidant enzymes was reduced in left ventricle in T4-50 and T4-75 groups and in right ventricle in the T4-75 group. Tempol reduced BP, plasma malondialdehyde, and total urinary excretion of F2 isoprostanes in hypertensive hyperthyroid rats but not in controls. Tempol did not improve cardiac hypertrophy, proteinuria, or creatinine clearance in hyperthyroid rats. In conclusion, the results obtained indicate that the activity of SOD, GPX, and GR in renal and cardiac tissues is decreased in hyperthyroidism and that antioxidant treatment with tempol ameliorates T4-induced hypertension.

Hypothyroid-associated central vestibular disease in 10 dogs: 1999-2005.

PubMed

Higgins, Michael A; Rossmeisl, John H; Panciera, David L

2006-01-01

With the exception of myxedema coma, central nervous system signs are rare in hypothyroid dogs. Central vestibular dysfunction is a possible and reversible manifestation of hypothyroidism. Medical records of dogs with vestibular dysfunction and hypothyroidism were reviewed. Of 113 records identified, 10 dogs with at least 2 concurrent clinical neurologic abnormalities localizable to the central vestibular system were included. Retrospective, descriptive study. Median age at diagnosis was 7 years (range, 5-10 years). All dogs were referred for progressive neurologic disease. Lesions were localized to the myelencephalic region in 5 dogs and to the vestibulocerebellum in 5 dogs. Two dogs had evidence of multifocal intracranial disease. Non-neurologic physical abnormalities suggestive of hypothyroidism were absent in 7 of 10 dogs. Hypercholesterolemia was the only consistent clinicopathologic abnormality detected, and was present in 7 of 10 dogs. All dogs had total thyroxine (TT4) and free thyroxine (fT4) concentrations below reference ranges, and 9 of 10 had increased TSH concentrations. Intracranial imaging studies were normal in 5 of 8 dogs, and identified lesions consistent with infarctions in 3 of 8 dogs. Albuminocytologic dissociation was detected in 5 of 6 CSF analyses. Brainstem auditory-evoked responses disclosed prolonged wave V latencies in 3 of 4 dogs tested. No other causes of central vestibular dysfunction were identified during other diagnostic investigations. The median time from initiation of treatment to clinical improvement was 4 days. Vestibular signs resolved in 9 of 10 dogs within 4 weeks. Although the pathogenesis in dogs without evidence of infarction is unknown, central vestibular dysfunction appears to be a rare but reversible neurologic sequelae of hypothyroidism.

The role of hypothyroidism in the etiology and progression of dilated cardiomyopathy in Doberman Pinschers.

PubMed

Beier, P; Reese, S; Holler, P J; Simak, J; Tater, G; Wess, G

2015-01-01

Hypothyroidism and dilated cardiomyopathy (DCM) are both common diseases in Doberman Pinschers. A possible influence of hypothyroidism on the etiology and progression of DCM is controversial. Evaluation of the role of hypothyroidism in etiology and progression of DCM. A total of 175 Doberman Pinschers. In this longitudinal prospective study, echocardiography and 24-hour ambulatory ECG recordings were performed in all dogs as screening tests for DCM. Total thyroxine (TT4 ) and thyroid ultrasonography served as initial screening tests for hypothyroidism and low TT4 values were followed up by a thyroid stimulating hormone (TSH) test or free total thyroxine (fT4 )/cTSH measurements. Additionally, a follow-up study of dogs affected by both DCM and hypothyroidism under optimal treatment for hypothyroidism was conducted. A total of 107 dogs were healthy, 45 dogs had DCM, 11 hypothyroidism, and 12 dogs had both DCM and hypothyroidism. TT4 values as well as the thyroid volumes were equivalent in the healthy dogs and in those with DCM. Neither ventricular premature complexes nor echocardiographic parameters differed between healthy and hypothyroid dogs. Dogs with DCM had a 2.26-fold (CI0.95 = 1.1-4.8) higher risk of also being affected by hypothyroidism. Despite optimal thyroid treatment of dogs with hypothyroidism and DCM, there was a progression of the heart disease. This study did not confirm a role of hypothyroidism in the etiology or progression of DCM. Treatment of hypothyroidism did not improve the clinical outcome. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Selective binding to transthyretin and tetramer stabilization in serum from patients with familial amyloidotic polyneuropathy by an iodinated diflunisal derivative

PubMed Central

2004-01-01

In familial amyloidotic polyneuropathy, TTR (transthyretin) variants are deposited as amyloid fibrils. It is thought that this process involves TTR tetramer dissociation, which leads to partially unfolded monomers that aggregate and polymerize into amyloid fibrils. This process can be counteracted by stabilization of the tetramer. Several small compounds, such as diclofenac, diflunisal and flufenamic acid, have been reported to bind to TTR in vitro, in the T4 (thyroxine) binding channel that runs through the TTR tetramer, and consequently are considered to stabilize TTR. However, if these agents bind plasma proteins other than TTR, decreased drug availability will occur, compromising their use as therapeutic agents for TTR amyloidosis. In the present work, we compared the action of these compounds and of new derivatives designed to increase both selectivity of binding to TTR and inhibitory potency in relation to TTR amyloid fibril formation. We found two diflunisal derivatives that, in contrast with diclofenac, flufenamic acid and diflunisal, displaced T4 from TTR in plasma preferentially over binding to albumin and thyroxine binding globulin. The same diflunisal derivatives also had a stabilizing effect on TTR tetramers in plasma, as studied by isoelectric focusing of whole plasma under semi-denaturing conditions. In addition, by transmission electron microscopy, we demonstrated that, in contrast with other proposed TTR stabilizers (namely diclofenac, flufenamic acid and diflunisal), one of the diflunisal derivatives tested efficiently inhibited TTR aggregation. Taken together, our ex vivo and in vitro studies present evidence for the selectivity and efficiency of novel diflunisal derivates as TTR stabilizers and as inhibitors of fibril formation. PMID:15080795

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

PubMed

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

2014-11-04

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

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

PubMed Central

Falconer, I R; Jacks, F

1975-01-01

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

Thyrotoxicosis induced by excessive 3,5,3'-triiodothyronine in a dog.

PubMed

Morré, Wendy A; Panciera, David L; Daniel, Gregory B; Refsal, Kent R; Rick, Markus; Arrington, Kathy

2017-06-15

CASE DESCRIPTION A 7-year-old castrated male Havanese was evaluated at a veterinary teaching hospital because of a 12-week history of hyperactivity, aggression, and progressive weight loss despite a healthy appetite. CLINICAL FINDINGS Tachycardia was the only remarkable finding during physical examination. Serum 3,5,3'-triiodothyronine (T3) and free T3 concentrations were markedly increased, and thyroxine (T4), free T4, and thyroid-stimulating hormone concentrations were at or decreased from the respective reference ranges. Thyroid scintigraphy revealed suppressed uptake of sodium pertechnetate Tc 99m by the thyroid gland but no ectopic thyroid tissue, which was indicative of thyrotoxicosis induced by an exogenous source of T3. TREATMENT AND OUTCOME The dog was hospitalized for 24 hours, and its diet was changed, after which the clinical signs rapidly resolved and serum T3 and free T3 concentrations returned to within the respective reference ranges. This raised suspicion of an exogenous source of T3 in the dog's home environment. Analysis of the commercial beef-based canned food the dog was being fed revealed a high concentration of T3 (1.39 μg/g) and an iodine (82.44 μg/g) concentration that exceeded industry recommendations. No other source of T3 was identified in the dog's environment. CLINICAL RELEVANCE To our knowledge, this is the first report of clinical thyrotoxicosis in a dog induced by exogenous T3, although the source of exogenous T3 was not identified. This case highlights the importance of measuring serum T3 and thyroid-stimulating hormone concentrations in addition to T4 and free T4 concentrations when there is incongruity between clinical findings and thyroid function test results.

[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.

Maternal hyperthyroidism is associated with a decreased incidence of cold-induced ascites in broiler chickens.

PubMed

Akhlaghi, A; Zamiri, M J; Zare Shahneh, A; Jafari Ahangari, Y; Nejati Javaremi, A; Rahimi Mianji, G; Mollasalehi, M R; Shojaie, H; Akhlaghi, A A; Deldar, H; Atashi, H; Ansari Pirsaraei, Z; Zhandi, M

2012-05-01

A hypothesis was tested that providing the breeder hens with exogenous thyroxine (T(4)) would help their offspring to better survive the ascites-inducing condition during the growing period. In total, 132 broiler breeder hens were randomly assigned to one of 3 treatments: control (CON), hypothyroid [HYPO; 6-N-propyl-2-thiouracil (PTU)-treated], and hyperthyroid (HYPER; T(4)-treated). The hens were artificially inseminated, and the hatching eggs (n = 1,320) were incubated. No eggs in the HYPO group hatched. The 1-d-old male chicks (n = 288) from other groups were reared for 42 d under standard or low ambient temperature to induce ascites. Blood samples were drawn from the hens, embryos, and broilers for determination of T(4) and triiodothyronine (T(3)). The hematocrit was also determined in broilers. The PTU-treated hens had an increased BW along with lower plasma T(3) and T(4) concentrations. Plasma T(4) was higher in the HYPER hens compared with CON hens, but T(3) concentration was not different between these groups. The fertility rate was not affected by either hypo- or hyperthyroidism. The embryos in the HYPO group had lower plasma T(3) and T(4) concentrations at d 18 of embryonic development and internal pipping. Higher plasma T(4) was recorded in the HYPER birds at internal pipping, although plasma T(3) concentration was not affected at this stage. Maternal hyperthyroidism decreased the overall incidence of ascites in the cold-exposed chickens (10.0 vs. 33.4% for HYPER and CON groups, respectively). Although the effect of maternal PTU or T(4) treatment on plasma thyroid hormones and on the right ventricle-to-total ventricular weight ratio in the broilers was not significant, the cold-exposed healthy CON chicks showed higher hematocrit values, compared with the HYPER birds. It was concluded that maternal hyperthyroidism could decrease the incidence of cold-induced ascites in broiler chickens; however, probable causal mechanisms remain to be elucidated.

Plasma Transthyretin as a Biomarker of Lean Body Mass and Catabolic States.

PubMed

Ingenbleek, Yves; Bernstein, Larry H

2015-09-01

Plasma transthyretin (TTR) is a plasma protein secreted by the liver that circulates bound to retinol-binding protein 4 (RBP4) and its retinol ligand. TTR is the sole plasma protein that reveals from birth to old age evolutionary patterns that are closely superimposable to those of lean body mass (LBM) and thus works as the best surrogate analyte of LBM. Any alteration in energy-to-protein balance impairs the accretion of LBM reserves and causes early depression of TTR production. In acute inflammatory states, cytokines induce urinary leakage of nitrogenous catabolites, deplete LBM stores, and cause an abrupt decrease in TTR and RBP4 concentrations. As a result, thyroxine and retinol ligands are released in free form, creating a second frontline that strengthens that primarily initiated by cytokines. Malnutrition and inflammation thus keep in check TTR and RBP4 secretion by using distinct and unrelated physiologic pathways, but they operate in concert to downregulate LBM stores. The biomarker complex integrates these opposite mechanisms at any time and thereby constitutes an ideally suited tool to determine residual LBM resources still available for metabolic responses, hence predicting outcomes of the most interwoven disease conditions. © 2015 American Society for Nutrition.

Thyroid Hormone Receptor α Mutation Causes a Severe and Thyroxine-Resistant Skeletal Dysplasia in Female Mice

PubMed Central

Bassett, J. H. Duncan; Boyde, Alan; Zikmund, Tomas; Evans, Holly; Croucher, Peter I.; Zhu, Xuguang; Park, Jeong Won

2014-01-01

A new genetic disorder has been identified that results from mutation of THRA, encoding thyroid hormone receptor α1 (TRα1). Affected children have a high serum T3:T4 ratio and variable degrees of intellectual deficit and constipation but exhibit a consistently severe skeletal dysplasia. In an attempt to improve developmental delay and alleviate symptoms of hypothyroidism, patients are receiving varying doses and durations of T4 treatment, but responses have been inconsistent so far. Thra1PV/+ mice express a similar potent dominant-negative mutant TRα1 to affected individuals, and thus represent an excellent disease model. We hypothesized that Thra1PV/+ mice could be used to predict the skeletal outcome of human THRA mutations and determine whether prolonged treatment with a supraphysiological dose of T4 ameliorates the skeletal abnormalities. Adult female Thra1PV/+ mice had short stature, grossly abnormal bone morphology but normal bone strength despite high bone mass. Although T4 treatment suppressed TSH secretion, it had no effect on skeletal maturation, linear growth, or bone mineralization, thus demonstrating profound tissue resistance to thyroid hormone. Despite this, prolonged T4 treatment abnormally increased bone stiffness and strength, suggesting the potential for detrimental consequences in the long term. Our studies establish that TRα1 has an essential role in the developing and adult skeleton and predict that patients with different THRA mutations will display variable responses to T4 treatment, which depend on the severity of the causative mutation. PMID:24914936

Functional and morphological changes in the adenohypophysis of dogs with induced primary hypothyroidism: loss of TSH hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement with transdifferentiation.

PubMed

Diaz-Espiñeira, M M; Mol, J A; van den Ingh, T S G A M; van der Vlugt-Meijer, R H; Rijnberk, A; Kooistra, H S

2008-07-01

From case studies in humans it is known that primary hypothyroidism (PH) may be associated with morphological and functional changes of the pituitary. There is no insight into the time scale of these changes. In this study, seven beagle dogs were followed up for 3 years after the induction of primary hypothyroidism. Three of these dogs were followed up for another 1.5 years while receiving l-thyroxine. Adenohypophyseal function was investigated at 2-month intervals with the combined intravenous injection of CRH, GHRH, GnRH, and TRH, and measurement of the plasma concentrations of ACTH, GH, LH, PRL, and TSH. In addition, after 2 years of hypothyroidism a single TRH-stimulation test and a somatostatin test were performed, with measurements of the same pituitary hormones. Every 6 months the pituitary gland was visualized by computed tomography (CT). Induction of PH led to high plasma TSH concentrations for a few months, where after concentrations gradually declined to values no longer significantly different from pre-PH values. A blunted response to stimulation of TSH release preceded this decline. Basal plasma GH concentrations increased during PH and there was a paradoxical hyperresponsiveness to TRH stimulation. Basal GH concentrations remained elevated and returned only to low values during l-thyroxine treatment. Basal PRL concentrations decreased significantly during PH and normalized after several months of l-thyroxine treatment. The pituitary gland became enlarged in all dogs. Histomorphology and immunohistochemical studies in 4 dogs, after 3 years of PH, revealed thyrotroph hyperplasia, large vacuolated thyroid deficiency cells, and decreased numbers of mammotrophs. Several cells stained for both GH and TSH. In conclusion, with time PH led to a loss of the TSH response to low T4 concentrations, hypersecretion of GH, and hyposecretion of PRL. The enlarged pituitaries were characterized by thyrotroph hyperplasia, large vacuolated thyroid deficiency cells, and double-staining cells, which are indicative of transdifferentiation.

A novel dendritic cell-based direct ex vivo assay for detection and enumeration of circulating antigen-specific human T cells.

PubMed

Carrio, Roberto; Zhang, Ge; Drake, Donald R; Schanen, Brian C

2018-05-07

Although a variety of assays have been used to examine T cell responses in vitro, standardized ex vivo detection of antigen-specific CD4 + T cells from human circulatory PBMCs remains constrained by low-dimensional characterization outputs and the need for polyclonal, mitogen-induced expansion methods to generate detectable response signals. To overcome these limitations, we developed a novel methodology utilizing antigen-pulsed autologous human dendritic target cells in a rapid and sensitive assay to accurately enumerate antigen-specific CD4 + T cell precursor frequency by multiparametric flow cytometry. With this approach, we demonstrate the ability to reproducibly quantitate poly-functional T cell responses following both primary and recall antigenic stimulation. Furthermore, this approach enables more comprehensive phenotypic profiling of circulating antigen-specific CD4 + T cells, providing valuable insights into the pre-existing polarization of antigen-specific T cells in humans. Combined, this approach permits sensitive and detailed ex vivo detection of antigen-specific CD4 + T cells delivering an important tool for advancing vaccine, immune-oncology and other therapeutic studies.

Ophthalmic Graves's disease: natural history and detailed thyroid function studies.

PubMed Central

Teng, C S; Yeo, P P

1977-01-01

Of 27 patients with ophthalmic Graves's disease (OGD) who had been clinically euthyroid three years previously, one became clinically hyperthyroid and seven overtly hypothyroid. Improvement in eye signs was associated with a return to normal of thyroidal suppression by triiodothyronine (T3) and of the response of thyroid-stimulating hormone (TSH) to thyrotrophin-releasing hormone (TRH). Of a further 30 patients with OGD who had not been studied previously, three were overtly hypothyroid. Of the combined series, 46 patients were euthyroid, 18 (40%) of whom had an impaired or absent TSH response to TRH, and 3(6-7%) an exaggerated response. Eleven out of 37 patients (29-7%) had abnormal results in the T3 suppression test. There was a significant correlation between thyroidal suppression by T3 and the TSH response to TRH. Total serum concentrations of both T3 and thyroxine (T4) were closely correlated with T3 suppressibility and TRH responsiveness. Free T4 and T3 (fT3) concentrations were normal in all but three patients, in whom raised fT3 was accompanied by abnormal TSH responses and thyroidal suppression. The presence of normal free thyroid hormone concentrations in patients with impaired or absent TSH responses to TRH is interesting and challenges the concept that free thyroid hormones are the major controlling factors in the feedback control of TSH. PMID:576414

Genetics Home Reference: inherited thyroxine-binding globulin deficiency

MedlinePlus

... Health Conditions Inherited thyroxine-binding globulin deficiency Inherited thyroxine-binding globulin deficiency Printable PDF Open All Close ... to view the expand/collapse boxes. Description Inherited thyroxine-binding globulin deficiency is a genetic condition that ...

21 CFR 862.1695 - Free thyroxine test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may...

21 CFR 862.1695 - Free thyroxine test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may...

21 CFR 862.1695 - Free thyroxine test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may...

21 CFR 862.1695 - Free thyroxine test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may...

21 CFR 862.1695 - Free thyroxine test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may...

Simultaneous quantification of T4, T3, rT3, 3,5-T2 and 3,3'-T2 in larval zebrafish (Danio rerio) as a model to study exposure to polychlorinated biphenyls.

PubMed

Chen, Xiaopeng; Walter, Kyla M; Miller, Galen W; Lein, Pamela J; Puschner, Birgit

2018-06-01

Environmental toxicants that interfere with thyroid hormone (TH) signaling can impact growth and development in animals and humans. Zebrafish represent a model to study chemically induced TH disruption, prompting the need for sensitive detection of THs. Simultaneous quantification of 3,3',5-triiodo-l-thyronine (T3), thyroxine (T4), 3,3',5'-triiodo-l-thyronine (rT3), 3,5-diiodo-l-thyronine (3,5-T2) and 3,3'-diiodo-l-thyronine (3,3'-T2) in zebrafish larvae was achieved by ultra-performance liquid chromatography-tandem mass spectrometry in positive ion mode. Solid-phase extraction with SampliQ cartridges and derivatization with 3 m hydrochloric acid in n-butanol reduced matrix effects. Derivatized compounds were separated on an Acquity UPLC BEH C 18 column with mobile phases consisting of 0.1% acetic acid in deionized water and 0.1% acetic acid in methanol. The limits of detection ranged from 0.5 to 0.6 pg injected on column. The method was validated by evaluating recovery (77.1-117.2%), accuracy (87.3-123.9%) and precision (0.5-12.4%) using diluted homogenized zebrafish embryos spiked with all target compounds. This method was then applied to zebrafish larvae collected after 114 h of exposure to polychlorinated biphenyls (PCBs), including PCB 28, PCB 66 and PCB 95, or the technical mixture Aroclor 1254. Exposure to PCB 28 and PCB 95 increased the T4:T3 ratio and decreased the T3:rT3 ratio, demonstrating that this method can effectively detect PCB-induced alterations in THs. Copyright © 2018 John Wiley & Sons, Ltd.

Changes of blood levels of several hormones, catecholamines, prostaglandins, electrolytes and cAMP in man during emotional stress.

PubMed

Tigranian, R A; Orloff, L L; Kalita, N F; Davydova, N A; Pavlova, E A

1980-01-01

The levels of several hormones (ACTH, GH, TSH, FSH, LH, parathyroid hormone--PTH, insulin, thyroxine--T4, triiodothyronine--T3, cortisol, testosterone, aldosterone, renin), catecholamines (epinephrine, norepinephrine, dopamin), prostaglandins (F1 alpha, F2 alpha, A + E), electrolytes (Na, K, Ca, Mg), cAMP and glucose in blood were measured before and immediately after the examination in 15 male students aged 28 to 35 years. Simultaneously the blood pressure was measured and hemodynamic measures were registered with the aid of echocardiography. A remarkable increase of catecholamines, ACTH, renin, T3, PTH, cAMP, PG F1 alpha, PG F2 alpha and Ca was found before the examination together with the increase of blood pressure. After the examination the levels of catecholamines, renin, aldosterone, T3, PTH, GH, FSH, LH, testosterone, PG A + E, glucose and Ca were found to be increased, while these of insulin, Na, PG F1 alpha, PG F2 alpha were decreased. The decrease of blood pressure was also found.

Increased Circulating Anti-inflammatory Cells in Marathon-trained Runners.

PubMed

Rehm, K; Sunesara, I; Marshall, G D

2015-10-01

Exercise training can alter immune function. Marathon training has been associated with an increased susceptibility to infectious diseases and an increased activity of inflammatory-based diseases, but the precise mechanisms are unknown. The purpose of this study was to compare levels of circulating CD4+  T cell subsets in the periphery of marathon-trained runners and matched non-marathon controls. 19 recreational marathoners that were 4 weeks from running a marathon and 19 demographically-matched healthy control subjects had the percentage of CD4+ T cell subpopulations (T helper 1, T helper 2, T helper 1/T helper 2 ratio, regulatory T cells, CD4+ IL10+, and CD4+ TGFβ+ (Transforming Growth Factor-beta) measured by flow cytometry. Marathon-trained runners had significantly less T helper 1 and regulatory T cells and significantly more T helper 2, CD4+ IL10+, and TGFβ+ cells than the control subjects. The alterations in the percentage of T helper 1 and T helper 2 cells led to a significantly lower T helper 1/T helper 2 ratio in the marathon-trained runners. These data suggest that endurance-based training can increase the number of anti-inflammatory cells. This may be a potential mechanism for the increased incidence of both infectious and inflammatory diseases observed in endurance athletes. © Georg Thieme Verlag KG Stuttgart · New York.

Studies of peripheral thyroxine distribution in thyrotoxicosis and hypothyroidism.

PubMed

Nicoloff, J T; Dowling, J T

1968-09-01

Compartmental analysis of the peripheral distribution of labeled thyroxine was applied to various groups of subjects with thyrotoxicosis and hypothyroidism. It was observed that the hepatic incorporation of thyroxine was augmented in subjects with Graves' disease when compared to non-Graves' disease control groups at all levels of thyroid function. Decreased values of hepatic incorporation occurred in primary hypothyroid subjects. These lowered values were not acutely corrected by elevation of the serum thyroxine level, but were observed to be rectified after several months' therapy with exogenous thyroid hormone. These alterations of the hepatic thyroxine-(131)I incorporation were independently verified by direct quantitative liver scintiscan determinations. Employing a dual thyroxine tracer system, we were able to demonstrate that during the early phases of equilibration of a tracer dose of thyroxine, alterations in the rate of deiodination were observed to be present in the various thyroid disease states. Increased deiodination rates were found in subjects with Graves' disease and the reverse was noted in patients with primary hypothyroidism. Kinetic analysis of thyroxine compartmental distribution during this early phase of equilibration of a labeled thyroxine tracer indicated that the primary tissue uptake occurred in the liver. These findings supported the contention that the amount of labeled thyroxine incorporated in the liver may be directly related to the deiodination rate of thyroxine by that organ. The pathogenetic basis of these alterations is presently unknown.

The role of selenium in iodine metabolism in children with goiter.

PubMed Central

Zagrodzki, P; Szmigiel, H; Ratajczak, R; Szybinski, Z; Zachwieja, Z

2000-01-01

Possible interactions between selenium and iodine metabolism were investigated in 7- to 16-year-old children with goiter (n = 136) living in southeastern Poland in iodine-deficient areas influenced by a sulfur industry. The Se-iodine interactions in these children were compared to the interactions in children from outside of that region (n = 38). Blood selenium (BSe) concentration and plasma glutathione peroxidase activity were much lower in the study group (64.1 +/- 15.7 microg/L; 111.0 +/- 27.6 U/L) than in the control group (85.3 +/- 19.6 microg/L; 182.4 +/- 35.6 U/L). Almost all of the data [plasma thyroid-stimulating hormone (TSH) concentration, plasma free thyroxine (fT(4)) concentration] fell within the reference limits. There was no statistically significant difference between the control and the study groups with respect to fT(4) and TSH. However, statistically significant differences of fT(4) and TSH in the study group were revealed between females belonging to the lower (n = 21; fT(4), 16.1 +/- 3.3 pmol/L; TSH, 1.83 +/- 1.05 mU/L) and upper Se quartiles (n = 24; fT(4), 14.5 +/- 2.2 pmol/L; TSH, 1. 26 +/- 0.90 mU/L), p < 0.05. Neither group differed in iodine in urine concentration, age, and body mass index. The difference in fT(4) concentrations can be attributed to an Se deficiency. The relationship exists only for females, which suggests a sex-linked hormonal response to concomitant Se and iodine deficiencies. Images Figure 1 Figure 2 PMID:10620526

Role of UDP-Glucuronosyltransferase (UGT) 2B2 in Metabolism of Triiodothyronine: Effect of Microsomal Enzyme Inducers in Sprague Dawley and UGT2B2-Deficient Fischer 344 Rats

PubMed Central

Richardson, Terrilyn A.; Klaassen, Curtis D.

2010-01-01

Microsomal enzyme inducers (MEI) that increase UDP-glucuronosyltransferases (UGTs) can impact thyroid hormone homeostasis in rodents. Increased glucuronidation can result in reduction of serum thyroid hormone and a concomitant increase in thyroid-stimulating hormone (TSH). UGT2B2 is thought to glucuronidate triiodothyronine (T3). The purposes of this study were to determine the role of UGT2B2 in T3 glucuronidation and whether increased T3 glucuronidation mediates the increased TSH observed after MEI treatment. Sprague Dawley (SD) and UGT2B2-deficient Fischer 344 (F344) rats were fed a control diet or diet containing pregnenolone-16α-carbonitrile (PCN; 800 ppm), 3-methylcholanthrene (3-MC; 200 ppm), or Aroclor 1254 (PCB; 100 ppm) for 7 days. Serum thyroxine (T4), T3, and TSH concentrations, hepatic androsterone/T4/T3 glucuronidation, and thyroid follicular cell proliferation were determined. In both SD and F344 rats, MEI treatments decreased serum T4, whereas serum T3 was maintained (except with PCB treatment). Hepatic T4 glucuronidation increased significantly after MEI in both rat strains. Compared with the other MEI, only PCN treatment significantly increased T3 glucuronidation (281 and 497%) in both SD and UGT2B2-deficient F344 rats, respectively, and increased both serum TSH and thyroid follicular cell proliferation. These data demonstrate an association among increases in T3 glucuronidation, TSH, and follicular cell proliferation after PCN treatment, suggesting that T3 is glucuronidated by other PCN-inducible UGTs in addition to UGT2B2. These data also suggest that PCN (rather than 3-MC or PCB) promotes thyroid tumors through excessive TSH stimulation of the thyroid gland. PMID:20421340

Status of oral ulcerative mucositis and biomarkers to monitor posttraumatic stress disorder effects in breast cancer patients.

PubMed

Loo, Wings T Y; Liu, Qing; Yip, Michael C W; Wang, Min; Chow, Louis W C; Cheung, Mary N B; Yip, Adrian Y S; Ng, Elizabeth L Y

2013-06-28

This study was designed to assess oral ulcerative mucositis, C-reactive protein, blood pressure, heart rate and thyroid function in breast cancer patients in relation to the occurrence of posttraumatic stress disorder 
(PTSD). A total of 120 female breast cancer patients and women 100 healthy subjects were enrolled in this study. PTSD status was assessed by questionnaire. Before and after treatment (modified radical mastectomy and chemotherapy), serum samples were collected and measured for levels of triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH) and high-sensitivity C-reactive protein (hs-CRP) by ELISA. Oral ulcerative mucositis was evaluated by the number and duration of oral ulcers and the degree of pain. Breast cancer patients experienced long-term PTSD and had elevated serum T3 and T4 levels. Patients experienced more severe pain and longer duration of oral ulcers compared with the healthy group. Oral ulcers were significantly associated with PTSD score in terms of the number of ulcers (p=0.0025), the degree of pain (p<0.0001) and the duration of ulcers (p<0.0001). These findings support that thyroid function is altered in breast cancer patients with PTSD. Elevation of T3 and T4 and oral ulcerative mucositis might be indicative of the emotional status of breast cancer patients.

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.

Successful every-other-day liothyronine therapy for severe resistance to thyroid hormone beta with a novel THRB mutation; case report.

PubMed

Maruo, Yoshihiro; Mori, Asami; Morioka, Yoriko; Sawai, Chihiro; Mimura, Yu; Matui, Katsuyuki; Takeuchi, Yoshihiro

2016-01-12

Resistance to thyroid hormone beta (RTHβ) is a rare and usually dominantly inherited syndrome caused by mutations of the thyroid hormone receptor β gene (THRB). In severe cases, it is rarely challenging to control manifestations using daily therapeutic replacement of thyroid hormone. The present case study concerns an 8-year-old Japanese girl with a severe phenotype of RTH (TSH, fT3, and fT4 were 34.0 mU/L, >25.0 pg/mL and, >8.0 ng/dL, respectively), caused by a novel heterozygous frameshift mutation in exon 10 of the thyroid hormone receptor beta gene (THRB), c.1347-1357 del actcttccccc : p.E449DfsX11. RTH was detected at the neonatal screening program. At 4 years of age, the patient continued to suffer from mental retardation, hyperactivity, insomnia, and reduced resting energy expenditure (REE), despite daily thyroxine (L-T4) therapy. Every-other-day high-dose liothyronine (L-T3) therapy improved her symptoms and increased her REE, without thyrotoxicosis. In a case of severe RTH, every-other-day L-T3 administration enhanced REE and psychomotor development, without promoting symptoms of thyrotoxicosis. Every-other-day L-T3 administration may be an effective strategy for the treatment of severe RTH.

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

EPA Pesticide Factsheets

The present study investigated whether inhibition of deiodinase, the enzyme which converts thyroxine (T4) to the more biologically-active form, 3,5,3'-triiodothyronine (T3), would impact inflation of the posterior and/or anterior chamber of the swim bladder, processes previously demonstrated to be thyroid-hormone regulated. Two experiments were conducted using a model deiodinase inhibitor, iopanoic acid (IOP). In the first study, fathead minnow (Pimephales promelas) embryos were exposed to 0.6, 1.9, or 6.0 mg IOP/L or control water in a flow-through system until reaching 6 days post-fertilization (dpf) at which time posterior swim bladder inflation was assessed. To examine effects on anterior swim bladder inflation, a second study was conducted with 6 dpf larvae exposed to the same IOP concentrations until reaching 21 dpf. Fish from both studies were sampled for T4/T3 measurements, gene transcription analyses, and thyroid histopathology. In the embryo study, incidence and length of inflated posterior swim bladders were significantly reduced in the 6.0 mg/L treatment at 6 dpf. Incidence of inflation and length of anterior swim bladder in larval fish were significantly reduced in all IOP treatments at 14 dpf, but inflation recovered by 18 dpf. Throughout the larval study, whole body T4 concentrations were significantly increased and T3 concentrations were significantly decreased in all IOP treatments. Consistent with hypothesized compensatory responses, sig

Estimation of Rapidly Exchangeable Cellular Thyroxine from the Plasma Disappearance Curves of Simultaneously Administered Thyroxine-131I and Albumin-125I*

PubMed Central

Oppenheimer, Jack H.; Bernstein, Gerald; Hasen, Julian

1967-01-01

A mathematical analysis of the plasma disappearance curves of simultaneously injected thyroxine-131I and albumin-125I allows the development of simple formulas for estimating the pool size and transfer kinetics of rapidly exchangeable intracellular thyroxine in man. Evidence is presented that the early distribution kinetics of albumin-125I can be used to represent the expansion of the thyroxine-131I-plasma protein complex into the extracellular compartment. Calculations indicate that approximately 37% of total body extrathyroidal thyroxine is within such exchangeable tissue stores. The average cellular clearance of thyroxine is 42.7 ml per minute, a value far in excess of the metabolic clearance of this hormone. Results of external measurements over the hepatic area and studies involving hepatic biopsies indicate that the liver is an important but probably not the exclusive component of the intracellular compartment. The partition of thyroxine between cellular and extracellular compartments is determined by the balance of tissue and plasma protein binding factors. The fractional transfer constants are inversely related to the strength of binding of each compartment and directly proportional to the permeability characteristic of the hypothetical membrane separating compartments. Appropriate numerical values for these factors are assigned. An increased fractional entrance of thyroxine-131I into the cellular compartment was noted in a patient with congenital decrease in the maximal binding capacity of thyroxine-binding globulin and in three patients after the infusion of 5,5-diphenylhydantoin. Decreased intracellular space and impaired permeability characteristics were observed in five patients with hepatic disease. Studies of the rate of entrance of thyroxine-131I and albumin-125I into the pleural effusion of a patient with congestive heart failure suggested that transcapillary passage of thyroxine independent of its binding protein is not a predominant factor in the total distribution kinetics of thyroxine-131I. The thesis is advanced that the distribution of thyroxine, both within the extracellular compartment and between the extracellular and intracellular compartments, is accomplished largely by the carrier protein and the direct transfer of thyroxine from one binding site to another. The concept of free thyroxine is reassessed in terms of this formulation. PMID:4960936

Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura

PubMed Central

Yu, Jin; Heck, Susanne; Patel, Vivek; Levan, Jared; Yu, Yu; Bussel, James B.

2008-01-01

Immune thrombocytopenic purpura (ITP) is characterized by the presence of antiplatelet autoantibodies as a result of loss of tolerance. CD4+CD25+ regulatory T cells (Tregs) are important for maintenance of peripheral tolerance. Decreased levels of peripheral Tregs in patients with ITP have been reported. To test whether inefficient production or reduced immunosuppressive activity of Tregs contributes to loss of tolerance in patients with chronic ITP, we investigated the frequency and function of their circulating CD4+CD25hi Tregs. We found a com-parable frequency of circulating CD4+CD25hiFoxp3+ Tregs in patients and controls (n = 16, P > .05). However, sorted CD4+CD25hi cells from patients with chronic ITP (n = 13) had a 2-fold reduction of in vitro immunosuppressive activity compared with controls (n = 10, P < .05). The impaired suppression was specific to Tregs as shown by cross-mixing experiments with T cells from controls. These data suggest that functional defects in Tregs contribute to breakdown of self-tolerance in patients with chronic ITP. PMID:18420827

Atrx deficiency induces telomere dysfunction, endocrine defects, and reduced life span

PubMed Central

Watson, L. Ashley; Solomon, Lauren A.; Li, Jennifer Ruizhe; Jiang, Yan; Edwards, Matthew; Shin-ya, Kazuo; Beier, Frank; Bérubé, Nathalie G.

2013-01-01

Human ATRX mutations are associated with cognitive deficits, developmental abnormalities, and cancer. We show that the Atrx-null embryonic mouse brain accumulates replicative damage at telomeres and pericentromeric heterochromatin, which is exacerbated by loss of p53 and linked to ATM activation. ATRX-deficient neuroprogenitors exhibited higher incidence of telomere fusions and increased sensitivity to replication stress–inducing drugs. Treatment of Atrx-null neuroprogenitors with the G-quadruplex (G4) ligand telomestatin increased DNA damage, indicating that ATRX likely aids in the replication of telomeric G4-DNA structures. Unexpectedly, mutant mice displayed reduced growth, shortened life span, lordokyphosis, cataracts, heart enlargement, and hypoglycemia, as well as reduction of mineral bone density, trabecular bone content, and subcutaneous fat. We show that a subset of these defects can be attributed to loss of ATRX in the embryonic anterior pituitary that resulted in low circulating levels of thyroxine and IGF-1. Our findings suggest that loss of ATRX increases DNA damage locally in the forebrain and anterior pituitary and causes tissue attrition and other systemic defects similar to those seen in aging. PMID:23563309

Effects of pre- and postnatal exposure to the UV-filter Octyl Methoxycinnamate (OMC) on the reproductive, auditory and neurological development of rat offspring

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

Axelstad, Marta, E-mail: maap@food.dtu.dk; Boberg, Julie; Hougaard, Karin Sorig

Octyl Methoxycinnamate (OMC) is a frequently used UV-filter in sunscreens and other cosmetics. The aim of the present study was to address the potential endocrine disrupting properties of OMC, and to investigate how OMC induced changes in thyroid hormone levels would be related to the neurological development of treated offspring. Groups of 14-18 pregnant Wistar rats were dosed with 0, 500, 750 or 1000 mg OMC/kg bw/day during gestation and lactation. Serum thyroxine (T{sub 4}), testosterone, estradiol and progesterone levels were measured in dams and offspring. Anogenital distance, nipple retention, postnatal growth and timing of sexual maturation were assessed. Onmore » postnatal day 16, gene expression in prostate and testes, and weight and histopathology of the thyroid gland, liver, adrenals, prostate, testes, epididymis and ovaries were measured. After weaning, offspring were evaluated in a battery of behavioral and neurophysiological tests, including tests of activity, startle response, cognitive and auditory function. In adult animals, reproductive organ weights and semen quality were investigated. Thyroxine (T{sub 4}) levels showed a very marked decrease during the dosing period in all dosed dams, but were less severely affected in the offspring. On postnatal day 16, high dose male offspring showed reduced relative prostate and testis weights, and a dose-dependent decrease in testosterone levels. In OMC exposed female offspring, motor activity levels were decreased, while low and high dose males showed improved spatial learning abilities. The observed behavioral changes were probably not mediated solely by early T{sub 4} deficiencies, as the observed effects differed from those seen in other studies of developmental hypothyroxinemia. At eight months of age, sperm counts were reduced in all three OMC-dosed groups, and prostate weights were reduced in the highest dose group. Taken together, these results indicate that perinatal OMC-exposure can affect both the reproductive and neurological development of rat offspring, which may be a cause of concern, as humans are systematically exposed to the compound through usage of sunscreens and other cosmetics.« less

B Cell Depletion Therapy Normalizes Circulating Follicular Th Cells in Primary Sjögren Syndrome.

PubMed

Verstappen, Gwenny M; Kroese, Frans G M; Meiners, Petra M; Corneth, Odilia B; Huitema, Minke G; Haacke, Erlin A; van der Vegt, Bert; Arends, Suzanne; Vissink, Arjan; Bootsma, Hendrika; Abdulahad, Wayel H

2017-01-01

To assess the effect of B cell depletion therapy on effector CD4+ T cell homeostasis and its relation to objective measures of disease activity in patients with primary Sjögren syndrome (pSS). Twenty-four patients with pSS treated with rituximab (RTX) and 24 healthy controls (HC) were included. Frequencies of circulating effector CD4+ T cell subsets were examined by flow cytometry at baseline and 16, 24, 36, and 48 weeks after the first RTX infusion. Th1, Th2, follicular Th (TFH), and Th17 cells were discerned based on surface marker expression patterns. Additionally, intracellular cytokine staining was performed for interferon-γ, interleukin (IL)-4, IL-21, and IL-17 and serum levels of these cytokines were analyzed. In patients with pSS, frequencies of circulating TFH cells and Th17 cells were increased at baseline compared with HC, whereas frequencies of Th1 and Th2 cells were unchanged. B cell depletion therapy resulted in a pronounced decrease in circulating TFH cells, whereas Th17 cells were only slightly lowered. Frequencies of IL-21-producing and IL-17-producing CD4+ T cells and serum levels of IL-21 and IL-17 were also reduced. Importantly, the decrease in circulating TFH cells was associated with lower systemic disease activity over time, as measured by the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index scores and serum IgG levels. B cell depletion therapy in patients with pSS results in normalization of the elevated levels of circulating TFH cells. This reduction is associated with improved objective clinical disease activity measures. Our observations illustrate the pivotal role of the crosstalk between B cells and TFH cells in the pathogenesis of pSS.

[Particular evolution of the thyroid state in Grave's disease: two cases].

PubMed

Cherif, Lotfi; Ben Abdallah, Néjib; Khairi, Karima; Hadj Ali, Inçaf; Turki, Sami; Ben Maïz, Hédi

2003-09-01

We report two cases of Grave's disease (GD) caracterized by the succession of hypothyroid and hyperthyroid states. Case 1: A 32 years old woman, has presented initially a typical GD with hyperthyroidism. Grave's ophtalmopathy and homogenous goiter. Four months later, she presented a spontaneous hypothyroidism necessiting treatment with thyroxine and a severe myasthenia gravis. More later (6 months), she experienced symptoms of hyperthyroidism after thymectomy. The level of anti-thyrotropin-receptor antibodies (TSab) was very high (141 UI/I, NV < 10). Case 2: A 29 years old woman has been treated by thyroxine (150 microg/day) for a primary hypothyroidism. Ten months later, she presented symptoms of hyperthyroidism even after stoppage of thyroxine. TSH value was decreased (TSH < 0.05 microU/ml) and FT4 level was raised (FT4 = 25.5 pmol/l). The thyroid antibodies were positive. We discuss, after review of the litterature, the physiopathological mecanisms of these changes in the thyroid state, particularly the role of the blocking and stimulating anti-thyrotropin-receptor antibodies.

The pathogenesis of propranolol-withdrawal syndrome in essential hypertension.

PubMed

Kristensen, B O; Steiness, E; Weeke, J

1979-12-01

1. In hypertension, the beta-adrenoreceptor-blocker-withdrawal syndrome comprises tachycardia, sweating, tremor and general malaise, symptoms resembling thyrotoxicosis. 2. The effect of abrupt cessation of propranolol on serum concentrations of thyroxine (T4) and triiodothyronine (T3) was therefore investigated in five patients with uncomplicated essential hypertension, treated with propranolol in doses from 160 to 480 mg/day. 3. Four of the five patients developed one or more of the above-mentioned symptoms within 2-6 days after withdrawal of propranolol. 4. A mean relative increase in serum free T3 of 51% (range 22-74%) was found in these four patients on the day of onset of symptoms. 5. The increase in free T3 in the five patients correlated positively with total serum propranolol on the last day the drug was given (r = 0.91, 2P = 0.03). 6. As an increase in T3 was found only in patients suffering the withdrawal syndrome, and was maximal the day the symptoms appeared, despite a variation in time of onset from 2 to 6 days, it is suggested that the beta-adrenoreceptor-blocker-withdrawal syndrome, at least partially, is caused by rebound increased production of T3, induced by the well-known inhibition of the monodeiodination of T4 to T3 during beta-adrenoreceptor blockade. 7. This assumption may explain the clinical symptoms and the reported transient increased beta-adrenoreceptor sensitivity with unchanged serum concentrations of catecholamines.

Severe hypothyroidism presenting as myxedema coma in the postoperative period in a patient taking sunitinib: case report and review of literature.

PubMed

Lele, Abhijit V; Clutter, Sarah; Price, Eleana; De Ruyter, Martin L

2013-02-01

The case of a 62-year-old Caucasian woman who underwent urgent hip hemiarthroplasty for repair of a pathological fracture is reported. The patient's medical history was significant for renal cell carcinoma, cerebellar metastases, and sunitinib-induced hypothyroidism. Her intraoperative course was complicated by profound hypothermia, bradycardia, augmentation of neuromuscular blockade, delayed emergence, failure of postoperative extubation, and need for mechanical ventilation. The intensive care course was significant for hypothermia requiring forced-air warming, treatment with intravenous thyroxine (T4), and hemodynamic supportive care. Copyright © 2013 Elsevier Inc. All rights reserved.