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This chapter details protocols for determining plasma thyroid hormone (TH) levels and tissue TH content by competitive radioimmunoassays (RIAs). These protocols include: an initial test of the chromatographic performance, isotopic labeling to produce high activity 125 I-T3 and 125 I-T4, free iodide estimation of the labeled products, purification of tracers from iodide by paper electrophoresis, extraction of THs from plasma and tissue samples, and the RIA procedures. The RIA involves the competition between radioactive labeled and unlabeled hormones for specific antibody binding, and due to its high sensitivity is capable of detecting a minimum of 2.5 pg of T4 and 0.4 pg of T3.Drs. María Jesús Obregon and Gabriella Morreale de Escobar improved these protocols in the 1970s, enhancing sensitivity and accuracy. Their improvements enabled the detection of TH content in tissues, providing crucial insights into maternal THs role in fetal development and the importance of iodine intake during gestation. Their research also facilitated the early detection of congenital hypothyroidism, preventing neurological impairments in newborns. Internationally and in Spain, their contributions are widely acknowledged, leading to substantial public health impacts, including the implementation of nationwide neonatal screening programs. Despite progress, thyroid diseases remain prevalent, underscoring the need for continued research into thyroid physiology and associated disorders, employing highly sensitive techniques like the RIA outlined herein that we continue using in our research., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

AbstractMaternal hormones, such as thyroid hormones (THs) transferred to embryos and eggs, are key signaling pathways for mediating maternal effects. To be able to respond to maternal cues, embryos must express the key molecular "machinery" of hormone pathways, such as enzymes and receptors. While altricial birds begin TH production only at or after hatching, experimental evidence suggests that their phenotype can be influenced by maternal THs deposited into the egg. However, it is not understood how or when altricial birds express genes in the TH pathway. For the first time, we measured the expression of key TH-pathway genes in altricial embryos by using two common altricial ecological model species, pied flycatcher ( Ficedula hypoleuca ) and blue tit ( Cyanistes caeruleus ). Deiodinase DIO1 gene expression could not be reliably confirmed in either species, but deiodinase enzyme genes DIO2 and DIO3 were expressed in both species. Given that DIO2 converts thyroxine to biologically active triiodothyronine and that DIO3 mostly converts triiodothyronine to inactive forms of THs, our results suggest that embryos may modulate maternal signals. TH receptors ( THRA and THRB ) and a monocarboxylate membrane transporter gene ( SLC16A2 ) were also expressed, enabling TH responses. Our results suggest that altricial embryos may be able to respond to and potentially modulate maternal signals conveyed by THs in early development.

A method for free thyroxine measurement in human serum using equilibrium dialysis followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) is described. Free thyroxine in serum is first separated from protein-bound thyroxine by equilibrium dialysis and then measured by LC-MS/MS., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Euryhaline fishes are capable of maintaining osmotic homeostasis in a wide range of environmental salinities. Several pleiotropic hormones, including prolactin, growth hormone, and thyroid hormones (THs) are mediators of salinity acclimation. It is unclear, however, the extent to which THs and the pituitary-thyroid axis promote the adaptive responses of key osmoregulatory organs to freshwater (FW) environments. In the current study, we characterized circulating thyroxine (T4) and 3-3'-5-triiodothyronine (T3) levels in parallel with the outer ring deiodination (ORD) activities of deiodinases (dios) and mRNA expression of dio1, dio2, and dio3 in gill during the acclimation of Mozambique tilapia (Oreochromis mossambicus) to FW. Tilapia transferred from seawater (SW) to FW exhibited reduced plasma T4 and T3 levels at 6 h. These reductions coincided with an increase in branchial dio2-like activity and decreased branchial dio1 gene expression. To assess whether dios respond to osmotic conditions and/or systemic signals, gill filaments were exposed to osmolalities ranging from 280 to 450 mOsm/kg in an in vitro incubation system. Gene expression of branchial dio1, dio2, and dio3 was not directly affected by extracellular osmotic conditions. Lastly, we observed that dio1 and dio2 expression was stimulated by thyroid-stimulating hormone in hypophysectomized tilapia, suggesting that branchial TH metabolism is regulated by systemic signals. Our collective findings suggest that THs are involved in the FW acclimation of Mozambique tilapia through their interactions with branchial deiodinases that modulate their activities in a key osmoregulatory organ., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Recent prescribing policies in England and Wales have imposed significant restrictions on liothyronine prescribing in general practice driven by the prohibitive costs and uncertain benefits of liothyronine in the management of hypothyroidism. However, the impact of these policies on liothyronine usage and costs is still unclear., Methods: Data were downloaded from the NHS monthly General Practice Prescribing Data in England and from the Comparative Analysis System for Prescribing Audit (CASPA) in Wales for 2011-2020. Trends over the period in amount and costs of levothyroxine and liothyronine prescribing were analysed., Results: The total medication costs per year for England Wales for hypothyroidism rose from £60.8 million to £129.8 million in 2015-16 and have since reduced to £88.4 million. Levothyroxine prescriptions have been growing above the population growth rate at 0.7%/annum in England and 1.1% in Wales. The costs/patient/year for liothyronine rose from £550 to £3000 in 2015-16 and has since fallen to £2500. Use of liothyronine as a percentage of levothyroxine started to fall in 2015-16 at 7%/annum in England and 3% in Wales. Nevertheless, 0.5% of levothyroxine-treated patients continue to receive liothyronine. All Clinical Commission Groups (CCGs) in England continue to have at least one liothyronine prescribing practice and 48.5% of English general practices prescribed liothyronine in 2019-20., Conclusion: In spite of strenuous attempts to limit prescribing of liothyronine in general practice, a significant number of patients continue to receive this therapy. The price differential of liothyronine vs levothyroxine should be examined again in light of the continuing use of liothyronine., (© 2021 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Identification of factors determining both of favorable and unfavorable outcome of IVF will increase the effectiveness of this method and optimize infertility treatment. The aim of the research is to analyze the correlation between serum IL-1α concentration, its gene rs1800587 (C/T) genotype carrier and thyroid-stimulating hormone (TSH), thyroid hormones (triiodothyronine (T3) and tetraiodothyronine (T4)), and evaluate the prognostic significance of their combinations in women with tube-peritoneal infertility under the IVF program. 120 patients with tube-peritoneal infertility who applied for an IVF program were examined. Depending on the outcome of the procedure, 2 groups of patients were allocated: 1 group - 40 women who had a pregnancy after IVF, 2 group - 80 patients who did not have a pregnancy. The content of IL-1α, TSH, T3, T4 was determined in blood by ELISA. Genotyping was performed on the rs1800587 (C/T) polymorphic marker of the IL-1α gene. TSH, T3, T4 were within the norm for both groups. In our study, women with a TSH concentration of 0.23 to 1.7 nmol/L had a chance of a favorable IVF outcome 1.4 times higher than with other TSH levels (p = 0.042901); with a T3 level of 1.0 to 1.8 nmol/L had a chance of becoming pregnant 5.7 times higher than with other levels of T3 (p = 0.00002). For T4 concentration, the confidence test was not achieved (p = 0.068505). The individual indicators of IL-1α, TSH, T3 and carrier of the genotype of the gene IL-1α at the preconceptive stage have lower diagnostic value than their combined combination. Three combinations have maximum predictive value: a combination of the T/T genotype of the IL-1α gene and the TSH level of 0.23 to 1.7 nmol/l - OR = 8.1 (p = 0.000048); combination of IL-1α of 28.7 to 85.1 pg/ml, T/T gene genotype IL-1α and TSH level of 0.23 to 1.7 nmol/l - OR = 8.1 (p = 0.000048); combination of IL-1α of 28.7 to 85.1 pg/ml, T/T gene genotype IL-1α, TSH level of 0.23 to 1.7 nmol/l and T3 level of 1.0 to 1.8 nmol/l - OR = 8.1 (p = 0.000146). Thus, proposed new prognostic markers of IVF program effectiveness., Competing Interests: The authors declare no conflict of interest.

Purpose: The purpose of the current study was to evaluate thyroid function in terms of serum thyroid-stimulating hormone (TSH, also known as thyrotropin), 3,5,3'-triiodo-L-thyronine (T3), and 3,5,3',5'-tetraiodo-L-thyronine (T4, also known as thyroxine) levels in migraineurs in comparison with non-migraineurs using a systematic review of literature and a meta-analysis., Methods: This is a systematic review of case-control studies on serum TSH, T3, and T4 concentrations of migraineurs in comparison with non-migraineurs. After extracting the data from the finally included studies, the weighted overall standardized mean difference (SMD) was calculated., Results: The weighted overall SMD for the impact of TSH, T3, and T4 blood levels for migraineurs in comparison with non-migraineurs was as follows: 0.804 (95% CI, 0.045-1.564), - 0.267 (95% CI, - 0.660-0.125), 0.093 (95% CI, - 0.077-0.263), respectively. It is noteworthy that only the p value for the significance of the overall SMD for serum TSH level was statistically significant (p = 0.038), as examined by the z-test., Conclusions: The results of the current study point to an association between migraine pathogenesis and changing TSH levels in comparison with those of controls.

Context: Physiological alterations challenge the assessment of maternal thyroid function in pregnancy. It remains uncertain how the reference ranges vary by week of pregnancy, and how the classification of disease varies by analytical method and type of thyroid function test., Design: Serum samples from Danish pregnant women (n = 6282) were used for the measurement of thyrotropin (TSH), total and free thyroxine (T4), total and free 3,5,3'-triiodothyronine (T3), and T-uptake using "Method A" (Cobas 8000, Roche Diagnostics). TSH and free T4 were also measured using "Method B" (ADVIA Centaur XP, Siemens Healthineers)., Main Outcome Measures: Pregnancy week- and method-specific reference ranges were established among thyroid antibody-negative women (n = 4612). The reference ranges were used to classify maternal thyroid function, and results were compared by analytical method and type of thyroid function test., Results: The reference ranges for TSH showed a gradual decrease during pregnancy weeks 4 to 14, a gradual increase was observed for total T4, total T3, and T-uptake, whereas free T4 and free T3 showed less variation. When TSH and free T4 were used, Method A classified 935 (14.9%) with abnormal thyroid function, Method B a total of 903 (14.4%), and the methods agreed on 554 individuals. When TSH and total T4 were used, 947 (15.1%) were classified with abnormal thyroid function, and classifications by either total T4 or free T4 agreed on 584 individuals., Conclusions: Even when pregnancy week- and method-specific reference ranges were established, the classification of maternal thyroid dysfunction varied considerably by analytical method and type of thyroid function test., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Guidelines on T4 + T3 combination therapy were published in 2012. This review investigates whether the issue is better understood 7 years later. Dissatisfaction with the outcome of T4 monotherapy remains high. Persistent symptoms consist mostly of fatigue, weight gain, problems with memory and thinking and mood disturbances. T4 monotherapy is associated with low serum T3 levels, which often require TSH-suppressive doses of L-T4 for normalization. Peripheral tissue thyroid function tests during T4 treatment indicate mild hyperthyroidism at TSH < 0.03 mU/L and mild hypothyroidism at TSH 0.3-5.0 mU/L; tissues are closest to euthyroidism at TSH 0.03-0.3 mU/L. This is explained by the finding that whereas T4 is usually ubiquinated and targeted for proteasomal degradation, hypothalamic T4 is rather stable and less sensitive to ubiquination. A normal serum TSH consequently does not necessarily indicate a euthyroid state. Persistent symptoms in L-T4 treated patients despite a normal serum TSH remain incompletely understood. One hypothesis is that a SNP (Thr92Ala) in DIO2 (required for local production of T3 out of T4) interferes with its kinetics and/or action, resulting in a local hypothyroid state in the brain. Effective treatment of persistent symptoms has not yet realized. One may try T4 + T3 combination treatment in selected patients as an experimental n = 1 study. The 2012 ETA guidelines are still valid for this purpose. More well-designed randomized clinical trials in selected patients are key in order to make progress. In the meantime the whole issue has become rather complicated by commercial and political overtones, as evident from skyrocketing prices of T3 tablets, aggressive pressure groups and motions in the House of Lords.

Thyroid hormones (THs; T3 and T4) play a role in development of cardiovascular, reproductive, immune and nervous systems. Thus, interpretation of TH changes from rodent studies (during pregnancy, in fetuses, neonates, and adults) is critical in hazard characterization and risk assessment. A roundtable session at the 2017 Society of Toxicology (SOT) meeting brought together academic, industry and government scientists to share knowledge and different perspectives on technical and data interpretation issues. Data from a limited group of laboratories were compiled for technical discussions on TH measurements, including good practices for reliable serum TH data. Inter-laboratory historical control data, derived from immunoassays or mass spectrometry methods, revealed: 1) assay sensitivities vary within and across methodologies; 2) TH variability is similar across animal ages; 3) laboratories generally achieve sufficiently sensitive TH quantitation levels, although issues remain for lower levels of serum TH and TSH in fetuses and postnatal day 4 pups; thus, assay sensitivity is critical at these life stages. Best practices require detailed validation of rat serum TH measurements across ages to establish assay sensitivity and precision, and identify potential matrix effects. Finally, issues related to data interpretation for biological understanding and risk assessment were discussed, but their resolution remains elusive., (Copyright © 2019. Published by Elsevier Inc.)

Objectives: This study aimed to establish the reference intervals (RIs) of thyroid function test among the adult Sudanese population in Khartoum, Sudan. A multi-stage survey stratified sampling method was used. Total triiodothyronine (TT3), total thyroxine (TT4) level and thyroid stimulating hormone (TSH) levels were measured using radioimmunoassay gamma counter (Riostad, Germany) to determine the reference intervals., Result: A total of 390 adults aged 20-75 years (male: 40.5%, female: 59.5%) were recruited. The median (95% intervals) serum TSH, TT4 and TT3 levels were 1.2 (0.50-3.1) mIU/L, 103.0 (63.0-159.0) nmol/L and 1.4 (0.8-2.7) nmol/L respectively. Compared with males; females had significantly lower TSH level and significantly higher TT4 level, but there was no significant difference when the TT3 level was assessed. While there was no significant difference in the level of TSH and T3 in the age group, T4 levels have shown a progressive increase with age. In summary the RIs for TSH, TT4 and TT3 in this setting were different from the levels provided by the manufacturers. A significant different was observed in TSH and FT4 when considering gender issue. The RIs were not different in the different age groups except for FT4.

Background: Hyperthyroidism is associated with alterations in metabolism that are currently only partially understood. The objective of the study was to investigate changes in metabolism associated with reinstatement of euthyroidism in Swedish patients., Methods: Eighty metabolites in plasma were profiled from 10 subjects with Graves' disease (GD) at baseline and after 9 and 15 months of treatment to reinstate euthyroidism. Thyroid parameters, thyrotropin (TSH), TSH receptor antibodies, free triiodothyronine, and free thyroxine were followed. Main findings were validated in plasma from 20 subjects with GD at baseline and at three, six, and nine months. The study was conducted at the endocrinology clinic in Malmö, Sweden., Results: Euthyroidism was reinstated at three months, and thyroid status did not change further during the 15-month follow-up. This was paralleled by altered levels of 9/19 detected acylcarnitines (p < 0.05 after adjustment for multiple testing). Levels of short-chain acylcarnitines were decreased, intermediate-chain acylcarnitines elevated, and long-chain acylcarnitines unaltered., Conclusions: GD and treatment of the disease is associated with pronounced acyl chain length-dependent alterations in acylcarnitine levels. These changes may be impacted by ethnicity and or dietary differences.

This study was conducted to determine plasma thyroxine (T4) concentrations in zoo-kept black-tailed prairie dogs ( Cynomys ludovicianus ). Thirty-one healthy prairie dogs of both sexes were studied as part of their annual clinical health evaluation, performed under general isoflurane anesthesia. Each animal underwent a complete physical examination, complete blood count, plasma biochemistry, and venous blood gas analysis. Heparinized venous blood samples were collected individually and processed for plasma T4 analysis using a veterinary biochemistry analyzer. The median plasma T4 concentration for the prairie dogs in this study was 4.1 μg/dl (minimum = 0.6 μg/dl; maximum = 8.0 μg/dl). The mean ± standard deviation plasma T4 concentration was 4.49 ± 2.39 μg/dl. No significant differences were found for varying ages, sexes, weights, or housing systems. The data presented in this report can promote better physiologic understanding and improve clinical management of this rodent species.

We describe the development and validation of multianalyte immunoassays (MAIA) for three analytes, viz., thyroxine (T4), thyroid stimulating hormone (TSH), and thyroglobulin (Tg) essential for assessment of thyroid function but having widely varying molecular weights. Using polycarbonate (PC) track-etched membranes (TEM) as an immobilization support and 125 I as the tracer, both competitive assay for T4 and non-competitive assay for TSH and Tg were performed on the same TEM. MAIA was found to be highly sensitive and precise with clinically useful working range and correlated very well with individual analyte immunoassays. While we have demonstrated this assay format with radiotracer, it can be used with non-isotopic tracers equally well.

Studies involving human genetic mutations and mutant mouse models have provided irrevocable evidence for a key role for thyroid hormones (THs) in the regulation of skeletal growth. While T3 binds to TH receptors with higher affinity than T4, T4 occupied TH receptors have also been reported in the nucleus under euthyroid conditions raising the possibility that T4 bound nuclear receptors may be biologically relevant in thyroid syndromes with elevated free T4 and reduced T3 levels. We, therefore, evaluated the direct effects of T4, T3, and their metabolites (rT3 and T2) in stimulating osteoblast differentiation using MC3T3-E1 preosteoblasts which do not produce detectable levels of deiodinases. Under serum-free conditions, a 24-h treatment of MC3T3-E1 cells with THs and their metabolites caused a dose-dependent increase in the expression of osteoblast differentiation markers, osterix, and osteocalcin. Circulating concentrations of T3 (~1 ng/ml) and T4 (~30 ng/ml) showed similar potency in stimulating osteoblast differentiation marker expression, while rT3 and T2 were less potent than T3 and T4. Moreover, T3 and T4 treatments elevated the IGF-1 mRNA level suggesting the involvement of IGF-1 signaling in the TH regulation of osteoblast differentiation. We conclude that an elevated T4 level in the absence of T3 may exert stimulatory effects on osteoblast differentiation. The establishment of cell-specific effects of T4 on osteoblasts may provide a strategy to generate T4 mimics that exert skeletal specific effects without the confounding T3 effects on other tissues.

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.)

Objective: 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., Study Design: 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., Results: 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., Conclusions: 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.)

Apoptosis is a key process associated with pathological cardiac remodelling in early-phase post-myocardial infarction. In this context, several studies have demonstrated an anti-apoptotic effect of thyroid hormones (TH). The aim of this study was to evaluate the effects of TH on the expression of proteins associated with the apoptotic process 14 days after infarction. Male Wistar rats (300-350 g) (n = 8/group) were divided into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated + TH (SHAMT) and infarcted + TH (AMIT). For 12 days, the animals received T3 and T4 [2 and 8 µg/(100 g day)] by gavage. After this, the rats were submitted to haemodynamic and echocardiographic analysis, and then were sacrificed and the heart tissue was collected for molecular analysis. Statistical analyses included two-way ANOVA with Student-Newman-Keuls post test. Ethics Committee number: 23262. TH administration prevented the loss of ventricular wall thickness and improved cardiac function in the infarcted rats 14 days after the injury. AMI rats presented an increase in the pro-apoptotic proteins p53 and JNK. The hormonal treatment prevented this increase in AMIT rats. In addition, TH administration decreased the Bax:Bcl-2 ratio in the infarcted rats. TH administration improved cardiac functional parameters, and decreased the expression of pro-apoptotic proteins 14 days after myocardial infarction.

Background: Weaning is a crucial period in the management of lambs, resulting in physiological and mental challenges, that may have prolonged effects on lamb's health and welfare., Hypothesis/objectives: To evaluate the effect of weaning on total and free triiodothyronine (T3, fT3) and thyroxine (T4, fT4) concentrations in serum of lambs by enzyme immunoassay. Animal and methods: The study was performed on two groups of 17 clinically healthy Comisana cross-bred lambs (7 males and 10 females) with or without weaning at 10 weeks of age. Serum samples were collected at the age of 8 weeks, 24 h and 2 weeks after weaning in the experimental group and at similar times in the non-weaned control group. Enzyme immunoassay was performed. Statistical analysis was done by one-way analysis of variance., Results: Compared to control animals, weaned animals showed significantly decreased T3 and elevated T4 concentrations two weeks after weaning with higher concentrations in both males and females in contrast to 24 h after weaning. Body weight (BW) was significantly restored in both females (11% increase) and males (6%) two weeks after weaning as compared to 24 h after weaning. No gender effects were shown for total and free iodothyronine changes. Significant positive correlations were observed between BW and T4 concentrations in both females (r = 0.692) and males (r = 0.856), fT3 concentrations in males (r = 0.968) and fT4 concentrations in females (r = 0.862)., Conclusion and Clinical Importance: Total iodothyronines could represent an indicator of their different metabolic activity with their magnitude altered two weeks following weaning.

Reactive oxygen species (ROS) are involved with progression from infarction to heart failure. Studies show that thyroid hormones (TH) present cardioprotective effects. This study aims to evaluate whether TH effects after infarction are associated to redox balance modulation. Male Wistar rats were divided into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated+TH (SHAMT), and infarcted+TH (AMIT). During 26 days, animals received T3 (2 μg/100g/day) and T4 (8 μg/100g/day) by gavage. Echocardiographic parameters were assessed and heart tissue was collected to biochemical analysis. AMIT rats presented absence of lung congestion, less cardiac dilatation, and normalization in myocardial performance index, compared with AMI. AMI rats presented an increase in hydrogen peroxide levels and in lipid peroxidation and a decrease in GSH/GSSG. TH prevented these alterations in AMIT. In conclusion, TH seem to reduce the levels of ROS, preventing oxidative stress, and improving cardiac function in infarcted rats., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Although thyroid-stimulating hormone (TSH) is known to be a major regulator of thyroid hormone biosynthesis and thyroid growth, insulin-like growth factor 1 (IGF-1) is required for mediating thyrocyte growth in concert with TSH in vitro. We generated mice with thyrocyte-selective ablation of IGF-1 receptor (TIGF1RKO) to explore the role of IGF-1 receptor signaling on thyroid function and growth. In 5-wk-old TIGF1RKO mice, serum thyroxine (T4) concentrations were decreased by 30% in concert with a 43% down-regulation of the monocarboxylate transporter 8 (MCT8), which is involved in T4 secretion. Despite a 3.5-fold increase in circulating concentrations of TSH, thyroid architecture and size were normal. Furthermore, thyrocyte area was increased by 40% in WT thyroids after 10 d TSH injection, but this effect was absent in TSH-injected TIGF1RKO mice. WT mice treated with methimazole and sodium perchlorate for 2 or 6 wk exhibited pronounced goiter development (2.0 and 5.4-fold, respectively), but in TIGF1RKO mice, goiter development was completely abrogated. These data reveal an essential role for IGF-1 receptor signaling in the regulation of thyroid function and TSH-stimulated goitrogenesis.

Timely diagnosis and treatment of thyroid dysfunction is compelling given the prevalence and severity of the disease. It requires reliance on adequate laboratory testing of serum TSH as a hallmark in combination with free thyroxine/triiodothyronine. Free hormone methods have to accommodate variations in the concentration and binding capacity of binding proteins. This is a challenge because none of the methodologies developed so far measures the actual unbound hormone in serum. The indirect methods provide an approximation while the direct ones estimate the free hormone concentration either in the presence of the protein-bound counterpart, or after physical separation of the free from bound fraction. The ongoing controversy on the validity and lack of comparability of methodologies points to their imperfectness to reflect real in-vivo free hormone concentrations. Therefore, laboratories and clinicians should know the window of validity and limitations of their methods. The recently developed reference measurement system is a key advance towards improved standardization and clinical validity of free thyroid hormone measurements., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Differential scanning calorimetry (DSC), mixed monomolecular layers and fluorescence spectroscopy techniques were applied to investigate the effect of thyroid hormones (THs) on the biophysical properties of model membranes. We found that both 3,3',5-triiodo-L-thyronine (T3) and 3,5,3',5'-tetraiodo-L-thyronine (T4) induce a broadening of the calorimetric main phase transition profile and reduce the transition enthalpy in liquid-crystalline state of dipalmitoylphosphatylcholine (DPPC) multilamellar vesicles. Tm changes from 41 °C to 40 °C compared to pure DPPC. When the experiments were done by adding THs to preformed multilamellar vesicles a second broader component in the DSC scan also appears at 20 min of incubation and becomes gradually more prominent with time, indicating a progressive alteration of lipid phase induced by THs. Analysis of surface pressure-molecular area isotherms in mixed monolayers of THs with either DPPC or 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) at air-water interface indicated a reduction in molecular area for THs/lipid mixtures at all surface pressures. A substantial decrease in surface potential in mixed lipid/THs monolayers at all surface pressures were observed for both phospholipids without affecting the mixed monolayer integrity. The data of mixed lipid/THs behavior support the establishment of lateral miscibility. Alterations of bidimensional liquid expanded→liquid condensed phase transition observed for DPPC/THs mixed monolayers are compatible with the changes observed in DSC. The transverse movement of THs and the decrease of dipole potential were also observed in single unilamellar vesicles by using appropriate fluorescent probes., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Transthyretin (TTR) is a protein whose aggregation and deposition causes amyloid diseases in human beings. Amyloid fibril formation is prevented by binding of thyroxin (T4) or its analogs to TTR. The MD simulation study of several solvated X-ray structures of apo and holo TTR has indicated the role of a conserved water molecule and its interaction with T4 binding residues Ser117 and Thr119. Geometrical and electronic consequences of those interactions have been exploited to design a series of thyroxin analogs (Mod1-4) by modifying 5' or 3' or both the iodine atoms of thyroxin. Binding energy of the designed ligands has been calculated by docking the molecules in tetrameric structure of the protein. Theoretically investigated pharmacological parameters along with the binding energy data indicate the potentiality of 3',5'-diacetyl-3,5-dichloro-l-thyronine (Mod4) to act as a better inhibitor for TTR-related amyloid diseases., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We present a comprehensive overview of changes in thyroxine (T4) and thyroid stimulating hormone (TSH) serum concentrations after pre-gestational, gestational and/or lactation exposures of rodents to various chemicals that affect the thyroid hormone system. We show that T4 and TSH changes consistent with the idealized view of the hypothalamic-pituitary-thyroid (HPT) feedback loop (T4 decrements accompanied by TSH increases) are observed with only a relatively small set of chemicals. Most substances affect concentrations of various thyroid hormones without increasing TSH. Studies of altered T4 concentrations after gestational exposures are limited to a relatively small set of chemicals in which pesticides, pharmaceuticals and industrial chemicals are under-represented. Our risk-of-bias analysis exposed deficits in T4/TSH analytics as a problem area. By relating patterns of T4 - TSH changes to mode-of-action (MOA) information, we found that chemicals capable of disrupting the HPT feedback frequently affected thyroid hormone synthesis, while substances that produced T4 serum decrements without accompanying TSH increases lacked this ability, but often induced liver enzyme systems responsible for the elimination of TH by glucuronidation. Importantly, a multitude of MOA leads to decrements of serum T4. The current EU approaches for identifying thyroid hormone system-disrupting chemicals, with their reliance on altered TH serum levels as indicators of a hormonal mode of action and thyroid histopathological changes as indicators of adversity, will miss chemicals that produce T4/T3 serum decreases without accompanying TSH increases. This is of concern as it may lead to a disregard for chemicals that produce developmental neurotoxicity by disrupting adequate T4/T3 supply to the brain, but without increasing TSH. [ABSTRACT FROM AUTHOR]

Thyrotropin-releasing hormone (TRH) stimulation can be used as a test of thyroid function and pituitary thyrotropin (thyroid-stimulating hormone, TSH) reserve, but optimal stimulation testing protocols in cats are unreported. We randomly divided 6 healthy young adult cats into 3 groups of 2 and administered 3 different intravenous doses of TRH (0.01, 0.05, 0.1 mg/kg) at weekly intervals in our crossover study. Serum TSH and thyroxine (T4) concentrations were measured using chemiluminescent immunoassay before, and at 30 and 60 min after, TRH administration. All cats were monitored for 4 h post-TRH administration for side effects. All 3 TRH doses induced significant TSH (0.01 mg/kg, p = 0.001; 0.05 mg/kg, p = 0.002; 0.1 mg/kg, p = 0.006) and total T4 (0.01 mg/kg, p = 0.008; 0.05 mg/kg, p = 0.006; 0.1 mg/kg, p = 0.001) responses. Lower TRH doses (0.01 and 0.05 mg/kg) caused fewer side effects (1 of 6 cats) than did the highest dose (3 of 6 cats), and may be safer in cats than the previously reported higher dose (0.1 mg/kg) of TRH. Our results do not support the use of maropitant to prevent side effects of a TRH stimulation test in cats. [ABSTRACT FROM AUTHOR]

BackgroundAntithyroid drugs, such as methimazole (MMI), are standard therapies for the medical management of thyrotoxicosis. Agranulocytosis is a rare but lethal adverse effect of antithyroid medications. We have reported 2 cases of MMI-induced agranulocytosis with similar risk factors that likely predisposed them to this adverse reaction.Case reportCase 1 involved a 71-year-old woman, with a history of Graves disease, who presented with an altered mental status. She was recently discharged on 40 mg of MMI twice daily, and she continued this dose for 2 months. She was readmitted and found to have neutropenic fever in the setting of MMI-induced agranulocytosis. MMI was discontinued, and she was started on filgrastim. Her cell counts gradually improved, and she was subsequently discharged.Case 2 involved a 68-year-old woman, with a history of Graves disease, who presented with severe back pain, nausea, and vomiting. She was recently discharged on 10 mg of MMI twice daily, which was increased to 10 mg 3 times a day. She was readmitted to the hospital because of a septic shock in the setting of pneumonia, colitis, bacteremia, and MMI-induced agranulocytosis. A bone marrow biopsy showed a polyclonal infiltrate with up to 85% plasma cells. Despite treatment with antibiotics, filgrastim, and continuous renal replacement therapy, she ultimately passed away.DiscussionAlthough these cases had differing outcomes, they shared similar features and risk factors, including older age, female sex, and relatively higher doses of MMI.ConclusionClose follow up and awareness of risk factors, such as age, female sex, and higher doses of MMI, may decrease the risk of MMI-induced agranulocytosis and fatal outcomes.

We present a comprehensive overview of changes in thyroxine (T4) and thyroid stimulating hormone (TSH) serum concentrations after pre-gestational, gestational and/or lactation exposures of rodents to various chemicals that affect the thyroid hormone system. We show that T4 and TSH changes consistent with the idealized view of the hypothalamic-pituitary-thyroid (HPT) feedback loop (T4 decrements accompanied by TSH increases) are observed with only a relatively small set of chemicals. Most substances affect concentrations of various thyroid hormones without increasing TSH. Studies of altered T4 concentrations after gestational exposures are limited to a relatively small set of chemicals in which pesticides, pharmaceuticals and industrial chemicals are under-represented. Our risk-of-bias analysis exposed deficits in T4/TSH analytics as a problem area. By relating patterns of T4 – TSH changes to mode-of-action (MOA) information, we found that chemicals capable of disrupting the HPT feedback frequently affected thyroid hormone synthesis, while substances that produced T4 serum decrements without accompanying TSH increases lacked this ability, but often induced liver enzyme systems responsible for the elimination of TH by glucuronidation. Importantly, a multitude of MOA leads to decrements of serum T4. The current EU approaches for identifying thyroid hormone system-disrupting chemicals, with their reliance on altered TH serum levels as indicators of a hormonal mode of action and thyroid histopathological changes as indicators of adversity, will miss chemicals that produce T4/T3 serum decreases without accompanying TSH increases. This is of concern as it may lead to a disregard for chemicals that produce developmental neurotoxicity by disrupting adequate T4/T3 supply to the brain, but without increasing TSH.

Background: Thyroid hormones are key determinants of health and well-being. Normal thyroid function is defined according to the standard 95% confidence interval of the disease-free population. Such standard laboratory reference intervals are widely applied in research and clinical practice, irrespective of age. However, thyroid hormones vary with age and current reference intervals may not be appropriate across all age groups. In this review, we summarize the recent literature on age-related variation in thyroid function and discuss important implications of such variation for research and clinical practice. Main text: There is now substantial evidence that normal thyroid status changes with age throughout the course of life. Thyroid stimulating hormone (TSH) concentrations are higher at the extremes of life and show a U-shaped longitudinal trend in iodine sufficient Caucasian populations. Free triiodothyronine (FT3) levels fall with age and appear to play a role in pubertal development, during which it shows a strong relationship with fat mass. Furthermore, the aging process exerts differential effects on the health consequences of thyroid hormone variations. Older individuals with declining thyroid function appear to have survival advantages compared to individuals with normal or high-normal thyroid function. In contrast younger or middle-aged individuals with low-normal thyroid function suffer an increased risk of adverse cardiovascular and metabolic outcomes while those with high-normal function have adverse bone outcomes including osteoporosis and fractures. Conclusion: Thyroid hormone reference intervals have differential effects across age groups. Current reference ranges could potentially lead to inappropriate treatment in older individuals but on the other hand could result in missed opportunities for risk factor modification in the younger and middle-aged groups. Further studies are now needed to determine the validity of age-appropriate reference intervals and to understand the impact of thyroid hormone variations in younger individuals. [ABSTRACT FROM AUTHOR]

PICO question In clinically hyperthyroid cats, is iodine-131 (I-131) treatment superior to unilateral or bilateral thyroidectomy in normalising serum thyroxine (T4) levels? Clinical bottom line Category of research question Treatment. The number and type of study designs reviewed 35 papers were critically reviewed. These were mostly retrospective studies with a small proportion of prospective cohort studies. Strength of evidence Moderate. Outcomes reported More papers were available evaluating the effect of radioiodine therapy on T4 levels compared to thyroidectomy. Long-term follow-up of T4 is a relatively new component of study designs. Most papers suggested between 40–87% cats had normal T4 6 months after treatment. 19–47% cats receiving unilateral or bilateral thyroidectomy, and 100% cats receiving radioiodine therapy were in long-term remission in one study. Conclusion In view of the evidence and outcomes from the studies, there is moderate evidence that I-131 treatment is superior to unilateral or bilateral thyroidectomy. How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Lead (Pb) is a prevalent environmental toxic metal that may harmfully affect the function of the thyroid gland. Our information about the effects of lead on thyroid function in lead poisoning is limited. The present study aimed to evaluate thyroid function in lead-poisoned patients compared with the healthy group. In this study, two groups of lead poisoning subjects (lead concentrations ≥ 25 μg/dL) (n = 56) (HBLC group) and randomly selected age and gender-matched healthy individuals with lower blood lead concentrations (BLC < 10 μg/dL) (n = 58) (LBLC group) were included. Thyroid function tests, including thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentration, were measured for each patient in both groups (for the HBLC group, it was taken on admission). The linear regression model was used to investigate the effects of lead poisoning on thyroid function tests. A p-value of less than 0.05 was considered significant. Our study showed no significant difference between the two groups in terms of age and gender. The mean concentration of T3 and TSH in the HBLC group was significantly lower than the LBLC group, but the mean levels of T4 were significantly higher in the HBLC group (p < 0.05). Based on the linear regression model results, the T3 and TSH levels in the LBLC group were significantly higher by 13.86 and 0.43 units than the HBLC group, respectively. The current study results showed that lead poisoning affects thyroid function, reduces TSH, and increases T4. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the correlation between triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) hormones and thyroid gland volume with volumetric analysis performed by using computed tomography (CT) images. In this retrospective study, IV contrasted thoracic CT images taken for different indications between 2019 January and 2020 January were scanned from the archive system of the hospital. 67 (31F, 36M) individuals chosen randomly among patients whose CT results were reported as normal and who had taken thyroid hormone tests within the past week were included in the study. Images in Digital Imaging and Communications in Medicine format were transferred to the personal work station program (Horos Medical Image Viewer). By using the Region of Interest (ROI) console in the current program, a three dimensional model was obtained by drawing the border of the thyroid gland in sections varying between 15 and 25. Volume values of this three-dimensional model and TSH, T3, T4 values of the individuals were compared. While no correlation was found between thyroid gland volume and T3 and T4 hormones, a negative significant correlation was found with TSH. In terms of gender, thyroid gland volume, T3, T4 values were found to be statistically significantly higher in women when compared with men (p≤0.05). TSH value was found to be higher in women when compared with men (p=0.005). No statistically significant difference was found in T4 value (p=0.057). Radio-anatomical volumetric data of the thyroid gland presented in this study and its correlation with thyroid functions will be beneficial to clinicians working in the field in both internal and surgical medicine branches and will also guide future studies. [ABSTRACT FROM AUTHOR]

Pesticides used massively in the agricultural sector would cause many poisoning and serious health problems. Organophosphate pesticides have been identified as endocrine-disrupting chemicals. This study aimed to compare thyroid hormone levels between the sprayers chronically exposed to pesticides and the control respondents who had never been exposed to pesticides. This study was an analytical observational with a cross-sectional design. The total number of respondents was 150, 50 as sprayers and 100 as control respondents. The venous blood samples were examined using the Enzyme-Linked Immunosorbent Assay (ELISA). The findings significantly showed that the sprayer had a higher level of thyroid-stimulating hormone (TSH) (4.776 ± 1.1166), lower triiodothyronine (T3) (108.822 ± 18.810), and lower thyroxine (T4) (7.808 ± 1.067). Determinant factors among sprayers that significantly correlated to TSH levels was age (p-value = 0.006); work duration (p-value = 0.000); personal protection equipment (PPE) (p-value = 0.045); body position (p-value = 0.014); type of pesticides (p-value = 0.004), correlated with T3 levels was age (p-value = 0.037); body position (p-value = 0.045), correlated with T4 levels was age (p-value = 0.000); PPE (p-value = 0.045). It could be concluded that chronic organophosphate exposure would increase TSH and decrease T3 and T4. [ABSTRACT FROM AUTHOR]

The evaluation of the thyroid can be a very involved process. A misinterpretation of the results of a thyroid function test can lead to serious complexities in a patient's management and outcome. The nuances in diagnostic approaches necessitates that standardized protocols for assessing thyroid function are established. A number of factors may impact how the thyroid functions and these factors must be considered when interpreting the results of a thyroid function test. Unfortunately, many clinicians only observe a cursory analysis of thyroid function. Primary care physicians, in particular, must be aware of these practice deficiencies and hopefully increase the detection of thyroid anomalies with greater accuracy at this first level of clinical contact.

Dichlorodiphenyltrichloroethane (DDT) and its metabolites accumulate in adipose tissue through dietary exposure, and have been proposed to contribute to the development of abdominal obesity, insulin resistance and dyslipidemia. Toxicity may also result when DDT and its metabolites are released from adipose tissue into the bloodstream as a result of rapid weight loss. We hypothesized that DDT-exposed rats fed a high fat diet (HFD) followed by 60% calorie restriction would have an adverse metabolic response to rapid weight loss. To test this, we exposed obese Sprague-Dawley (SD) rats to DDT and a HFD over one month followed by 60% calorie restricted diet for two weeks, and examined metabolic parameters throughout the study. During the HFD feeding period, DDT-exposed rats had significantly elevated postprandial non-esterified fatty acids (NEFAs) and decreased body temperature compared with control rats. During calorie restriction, DDT-exposed rats had lowered food efficiency (weight gained/calories consumed), body temperature, and circulating TSH. Our findings suggest that exposure to DDT may impairs metabolic substrate utilization in rats during dynamic periods of weight gain and weight loss.

The evaluation of the thyroid can be a very involved process. A misinterpretation of the results of a thyroid function test can lead to serious complexities in a patient's management and outcome. The nuances in diagnostic approaches necessitates that standardized protocols for assessing thyroid function are established. A number of factors may impact how the thyroid functions and these factors must be considered when interpreting the results of a thyroid function test. Unfortunately, many clinicians only observe a cursory analysis of thyroid function. Primary care physicians, in particular, must be aware of these practice deficiencies and hopefully increase the detection of thyroid anomalies with greater accuracy at this first level of clinical contact. [ABSTRACT FROM AUTHOR]

Psoriasis in general wide distribution disease around the world. It is manifested by the persistence of chronic inflammatory disorders, that's characterized by increased erythrocyte sedimentation rate percent(ESR). A previous of absolute outcomes evidence proved an elevation level of thyroid hormones in psoriatic patients. However, the present study aimed to investigate the contribution of thyroid hormones in psoriasis severity disease and their interact relation with intensive inflammation pathways in those of chronic psoriasis disease. Determination of thyroid stimulating hormone (TSH), thyroxine (T4) and triiodothyronine (T3) in 50 psoriasis patients and 40 healthy control groups in the case-control study were done by use Enzyme Linked Fluorescent Assay (ELFA). TSH, T4, T3, and ESR found to significantly increase in comparison with healthy controls. In conclusion, thyroid hormones are induced by elevated levels of TSH. Thyroid hormones affect the rate of keratinocyte division and therefore keeps the disease in an active stage. [ABSTRACT FROM AUTHOR]

Background: Whilst trials of combination levothyroxine/liothyronine therapy versus levothyroxine monotherapy for thyroid hormone replacement have not shown any superiority, there remains a small subset of patients who do not feel well on monotherapy. Whilst current guidelines do not suggest routine use of combination therapy they do acknowledge a trial in such patients may be appropriate. It appears that use of combination therapy and dessicated thyroid extract is not uncommon but often being used by non-specialists and not adequately monitored. This review aims to provide practical advice on selecting patients, determining dose and monitoring of such a trial. Main body: It is important to select the correct patient for a trial so as to not delay diagnosis or potentially worsen an undiagnosed condition. An appropriate starting dose may be calculated but accuracy is limited by available formulations and cost. Monitoring of thyroid function, benefits and adverse effects are vital in the trial setting given lack of evidence of safe long term use. Also important is that patients understand set up of the trial, potential risks involved and give consent. Conclusion: Whilst evidence is lacking on whether a small group of patients may benefit from combination therapy a trial may be indicated in those who remain symptomatic despite adequate levothyroxine monotherapy. This should be undertaken by clinicians experienced in the field with appropriate monitoring for adverse outcomes in both short and long term. [ABSTRACT FROM AUTHOR]

The application of nanoparticles in medicine is an attractive proposition. In this study, copper iodide nanoparticles (CuI NPs) were tested in vivo, 24 male of albino mice were distributed randomly to four groups, the result of group III (treated) showed significant decreasing (P ≤ 0.05) of thyroxin (T4) and also stimulating thyroid hormone (TSH) level with significant increasing (P ≤ 0.05) in triidothyronine (T3) compared with negative control and positive control groups. While the result of group IV(mixed) showed significant decreasing (P ≤ 0.05) of T4 and TSH compared with negative control and positive control, whereas T3 was not affected. [ABSTRACT FROM AUTHOR]

Thyroid hormones (THs) are essential for fetal and postnatal nervous system development and also play an important role in the maintenance of adult brain function. Of the two major thyroid hormones, T4 (3,5,3',5' tetra-iodo-L-thyronine) is classically viewed as an pro-hormone that must be converted to T3 (3,5,3' tri-iodo-L-thyronine) via tissue-level deiodinases for biological activity. THs primarily mediate their effects by binding to thyroid hormone receptor (TR) isoforms, predominantly TRα1 and TRβ1, which are expressed in different tissues and exhibit distinctive roles in endocrinology. Notably the ability to respond to T4 and to T3 differs for the two TR isoforms, with TRα1 generally more responsive to T4 than is TRβ1. TRα1 is also the most abundantly expressed TR isoform in the brain, encompassing 70-80% of all TR expression in this tissue. Conversion of T4 into T3 via deiodinase 2 in astrocytes has been classically viewed as critical for generating local T3 for neurons. However, deiodinase-deficient mice do not exhibit obvious defectives in brain development or function. Considering that TRα1 is well established as the predominant isoform in brain, and that TRα1 responds to both T3 and T4, we suggest T4 may play a more active role in brain physiology than has been previously accepted.

Prevalence of subclinical hypothyroidism in HIV-positive patients is reported to be high in those with severe immune deficiency. However, there is paucity of literature in newly-diagnosed HIV-positive population. Our aim was to estimate the prevalence of thyroid dysfunction and study its correlation with CD4 count in this population. In this cross-sectional study, patients presenting to the antiretroviral therapy clinic were screened with thyroid function tests, including thyroid stimulating hormone, free triiodothyronine, free thyroxine, and anti-thyroid peroxidase antibody levels at the time of diagnosis. Two hundred and twenty-five HIV-positive and an equal number of healthy volunteers were enrolled. The mean (SD) CD4 count in the study group was 147.1 (84) and 70.7% had advanced immune deficiency with CD4 count <200 cells/µL. The overall prevalence of thyroid dysfunction was 75.5% in the study group and 16% in the control group. Subclinical hypothyroidism was the commonest abnormality noted in almost 53%. Significant correlation was observed between CD4 count and thyroid stimulating hormone, free triiodothyronine, and free thyroxine levels (r = -0.86, r = 0.77, and r = 0.84, respectively, p < 0.0001 for all). The present study demonstrated high prevalence of thyroid dysfunction in HIV-positive patients. The dysfunction is subclinical in most cases and correlates well with declining CD4 counts. [ABSTRACT FROM AUTHOR]

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1. The liver metabolizes thyroxine (T4) through two major pathways: deiodination and conjugation. Following exposure to xenobiotics, T4 conjugation increases through the induction of hepatic uridine diphosphate glucuronosyltransferase (UGT) in rodents; however, it is uncertain to what degree different species employ deiodination and conjugation in the metabolism of T4. The objective of this study was to compare the metabolism of T4 in untreated and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB 153)-treated primary sandwich-cultured hepatocytes from rat (SCRH) and human (SCHH). 2. Basal metabolite concentrations were 13 times higher in the medium of SCRH compared to SCHH. Metabolite distribution in the medium of SCRH versus SCHH was as follows: T4G, (91.6 versus 5.3%); T4S, (3.6 versus 4.4%) and T3 + rT3, (4.9 versus 90.3%). PCB 153 induced T4G in the medium of SCRH and SCHH; however, T4S and T3 + rT3 were changed but to a much lesser degree. 3. The results indicate that baseline T4 glucuronidation is greater in SCRH compared to SCHH. These data also suggest that glucuronidation may be a more important pathway for T4 metabolism in rats and deiodination may be a favored pathway in humans; however, with PCB 153 treatment these data support glucuronidation as a primary route of T4 metabolism in both rat and humans. [ABSTRACT FROM AUTHOR]

Abstract: Previous work has shown that exposure to bisphenol A (BPA) can affect anxiety behavior. However, no studies have examined whether administration of this endocrine disruptor during the perinatal period has the potential to induce alterations in cognitive behavior in both adult males and females as assessed in an appetitive task. The goal of the current study was to determine whether exposure to different doses of BPA during early development alters performance on the 17-arm radial maze in adulthood in Long–Evans rats. Oral administration of corn oil (vehicle), 4μg/kg, 40μg/kg, or 400μg/kg BPA to the dams occurred daily throughout pregnancy, and the pups received direct oral administration of BPA between postnatal days 1–9. Blood was collected from offspring at weaning age to determine levels of several hormones (thyroxine, thyroid stimulating hormone, follicle stimulating hormone, luteinizing hormone). One male and one female from each litter were evaluated on the 17-arm radial maze, a working/reference memory task, in adulthood. Results indicated that after exposure to BPA at both 4 and 400μg/kg/day, rats of both sexes had decreased levels of FSH at weaning. There were no significant effects of BPA on performance on the radial arm maze in males or females. In conclusion, exposure to BPA during early development had modest effects on circulating hormones but did not affect performance on a spatial learning and memory task. [Copyright &y& Elsevier]

In this study, thermal stress adaptation capabilities in the event of changes resulting from hormonal mechanism, yield levels of Saanen goats and native Hair goats, were determined in humid subtropical climate conditions. The both genotypes were kept in same conditions at breeders condition. The Saanen goats were distributed within the microJprojects in the province of Adana. To find out thermal stress effects on T3, T4 hormone levels and milk production, 20 heads Saanen goats and 20 heads native Hair goats of Karaisalı district of the province of Adana were investigated in this study during July. In this study, when the mechanisms of physiological adaptation and serum T3 and T4 hormone levels taken together to consideration, the stress conditions of imported Saanen goats occurred when they were compared to indigenous Hair of goats. Thus it could be said that, Saanen goats did not show the expected performance. Therefore, as a conclusion of this study, it should be underlined that, the importance of environmental and regional conditions for this kind of improvement studies should have been taken into considerations. [ABSTRACT FROM AUTHOR]