Plasma Free T4 Research Articles

Determination of the regulatory properties of Yucca schidigera extracts on the biochemical parameters and plasma hormone levels associated with obesity

Yucca schidigera Ortgies, Asparagaceae, is a herbaceous plant. Due to the high saponin content the powdered branches and leaves are used as natural food additive for human and animal. The aim of this study was to investigate the effects of Y. schidigera extracts on plasma leptin, ghrelin, adiponectin, insulin, thyroid hormones and some biochemical parameters in mice fed a high-fat diet. Male Swiss Albino mice were divided into seven equal groups. Group I (negative control group) was given standard diet; Group II was given high-fat diet; Group III was given high-fat diet with carboxymethylcellulose; Groups IV–VII were given hexane, petroleum ether, ethyl acetate, and methanol extracts of Y. schidigera and high-fat diet via gastric gavage for 60 days. High-fat diet significantly increased plasma leptin, insulin, free T3 hormone, glucose, cholesterol, low-density lipoprotein, triacylglyceride, aspartate aminotransferase and alanine aminotransferase levels, and significantly decreased plasma ghrelin, adiponectin and free T4 hormone levels. On the other hand, hormone levels, lipid profile and biochemical parameters were improved by the administration of the PE extract. Y. schidigera extracts could be used as preventive medicine in nutritional disorders via regulating energy metabolism and hormonal functions.

The effect of maternal nutrition level during the periconception period on fetal muscle development and plasma hormone concentrations in sheep

The effect of maternal nutrition level during the periconception period on the muscle development of fetus and maternal–fetal plasma hormone concentrations in sheep were examined. Estrus was synchronized in 55 Karayaka ewes and were either fed ad libitum (well-fed, WF, n=23) or 0.5×maintenance (under-fed, UF, n=32) 6 days before and 7 days after mating. Non-pregnant ewes (WF, n=13; UF, n=24) and ewes carrying twins (WF, n=1) and female (WF, n=1; UF, n=3) fetuses were removed from the experiment. The singleton male fetuses from well-fed (n=8) and under-fed (n=5) ewes were collected on day 90 of gestation and placental characteristics, fetal BWs and dimensions, fetal organs and muscles weights were recorded. Maternal (on day 7 after mating) and fetal (on day 90 of pregnancy) blood samples were collected to analyze plasma hormone concentrations. Placental characteristics, BW and dimensions, organs and muscles weights of fetuses were not affected by maternal feed intake during the periconception period. Maternal nutrition level did not affect fiber numbers and the muscle cross-sectional area of the fetal longissimus dorsi (LD), semitendinosus (ST) muscles, but the cross-sectional area of the secondary fibers in the fetal LD and ST muscles from the UF ewes were higher than those from the WF ewes (P<0.05). Also, the ratio of secondary to primary fibers in the ST muscle were tended to be lower in the fetuses from the UF ewes (P=0.07). Maternal nutrition level during the periconception period did not cause any significant changes in fetal plasma insulin and maternal and fetal plasma IGF-I, cortisol, progesterone, free T3 and T4 concentrations. However, maternal cortisol concentrations were lower while insulin concentrations were higher in the WF ewes than those in the UF ewes (P<0.05). These results indicate that the reduced maternal feed intake during the periconception period may alter muscle fiber diameter without affecting fiber types, fetal weights and organ developments and plasma hormone concentrations in the fetus.

Plasma thyroid hormone concentration is associated with hepatic triglyceride content in patients with type 2 diabetes

The underlying mechanisms responsible for the development and progression of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) are unclear. Since the thyroid hormone regulates...

Biochemical and molecular investigation of thermal manipulation protocols during broiler embryogenesis and subsequent thermal challenge.

BackgroundThe aim of the current study was to evaluate the effect of different thermal manipulation (TM) protocols during embryogenesis on thermotolerance acquisition parameters during subsequent thermal challenge (TC) at posthatch day 28. A total of 1500 fertile chicken eggs were divided randomly into five treatments (300 eggs each): control was maintained at 37.8 °C and 56 % relative humidity (RH) whereas, TM1, TM2, TM3 and TM4 were subjected to 38.5, 39, 39.5 and 40 °C for 18 h and 65 % RH daily during embryonic days ED 12–18. Hatched chicks from each treatment group allocated randomly into two sub-treatment groups (thermo-neutral, naïve (TN) and thermal challenge (TC). At day 28 of age, chicks subjected to TC by adjusting room temperature to 42 °C for 6 h while naïve chicks kept under regular conditions (22 ± 1 °C and 50–60 % RH). Chick’s response to TC evaluated by determination of plasma T3, T4, corticosterone, total proteins, albumin, selected enzymes and some electrolytes at the beginning (0 h) and after 1, 3 and 5 h of TC in TM and TN chicks. Furthermore, pectoral and thigh muscles mRNA expression of Atrogin-1, CK, avUCP, DIO3, DIO2 were evaluated in TC and TN sub-treatment groups.ResultsTM induced a significant reduction in free T3 and elevation in total proteins and albumin in plasma with significant down-regulation of Atrogin-1 and DIO2 and significant up-regulation of DIO3 mRNA expression in muscle of TM chicks compare to control. During TC at day 28, decrease in the concentrations of plasma free T3, total proteins and albumin with increase in T4 have been detected in control and TM chicks. TC induced up-regulation of Atrogin-1 and DIO3 with down-regulation of DIO2 gene expression in muscles of all TC chicks.ConclusionThe present study indicated that, TM improved thermotolerance acquisition by decreasing basal metabolic rate and muscle injury during thermal stress. Basal metabolic rate decreased via reduction of plasma T3 concentration with up and down regulation of expression of DIO3 and DIO2, respectively in muscles. Muscle injury protected by stimulation of protein biosynthesis and down-regulation of Atrogin-1 expression.

EFFECT OF SELENIUM SUPPLEMENTATION VIA BRAZIL NUT (BERTHOLLETIA EXCELSA, HBK) ON THYROID HORMONES LEVELS IN HEMODIALYSIS PATIENTS: A PILOT STUDY.

thyroid function depends on trace mineral selenium (Se), being at the active center of the iodothyronine deiodinase that catalyzes the conversion of the thyroxine (T4) to the active form of thyroid hormone, triiodothyronine (T3). Hemodialysis (HD) patients have reduced T3 levels partly due to impaired hormonal conversion that can be related to Se deficiency, a common feature in these patients. This study evaluated the effect of Brazil nuts (richest Se source) on thyroid hormone levels in HD patients. we performed an uncontrolled intervention with 40 HD patients (53.3 ± 16.1 yrs, dialysis vintage 62.0 (8.0 - 207.0) months) that received one nut (≈5g, average 58.1 μg Se/g) per day for three months. Se plasma levels were determined by atomic absorption spectrophotometry with hydride generation and, serum T3, free T4 (FT4), TSH as well as glutathione peroxidase (GPx) activity were measured by ELISA. all patients were Se deficient and presented low T3 levels at baseline. After intervention, Se plasma levels (from 17.6 ± 11.6 to 153.4 ± 86.1 μg/L), GPx activity (from 33.7 ± 5.9 to 41.4 ± 11.2 nmol/min/mL), T3 (from 27.3 ± 8.8 to 50.2 ± 4.8ng/dL) and FT4 levels (0.87 ± 0.2 to 0.98 ± 0.4 ng/dL) were significantly increased (p < 0.05), while TSH levels were reduced (from 2.17 ± 1.3 to 1.96 ± 1.1 uUI/mL), but not significantly. in conclusion, increasing Se levels via Brazil nut supplementation was associated with improvement in thyroid hormone levels in HD patients, although the amount of Se given was not able to restore T3 to normal levels.

Low T3 syndrome and long-term mortality in chronic hemodialysis patients.

To investigate the predictive value of low freeT3 for long-term mortality in chronic hemodialysis (HD) patients and explore a possible causative role of chronic inflammation. One hundred fourteen HD patients (84 males) consecutively entered the study and were assessed for thyroid function and two established markers of inflammation, high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). Monthly blood samples were obtained from all patients for three consecutive months during the observation period for evaluation of thyroid function and measurement of inflammatory markers. The patients were then divided in two groups based on the cut-off value of 1.8 pg/mL for mean plasma freeT3, and were prospectively studied for a mean of 50.3 ± 30.8 mo regarding cumulative survival. The prognostic power of low serum fT3 levels for mortality was assessed using the Kaplan-Meier method and univariate and multivariate regression analysis. Kaplan-Meier survival curve showed a negative predictive power for low freeT3. In Cox regression analysis low freeT3 remained a significant predictor of mortality after adjustment for age, diabetes mellitus, hypertension, hsCRP, serum creatinine and albumin. Regarding the possible association with inflammation, freeT3 was correlated with hsCRP, but not IL-6, and only at the first month of the study. In chronic hemodialysis patients, low plasma freeT3 is a significant predictor of all-cause mortality. Further studies are required to identify the underlying mechanisms of this association.

Oestrogen Receptor Alpha and Progesterone Receptor in Uterus and Ovaries on Different Days of The Oestrus Cycle in Hyperthyroid Rats

Background: The present study evaluated, in different oestrus cycle phases, the oestrogen receptor alpha (ERα) and progesterone receptor (PgR) in rates with hyperthyroid ovaries and uterus.Materials and Methods: Sixty-four adult female wistar albino rats were used. Animals were randomly separated into eight different groups, four of which constituted the control group and the other four of which were the actual experimental group. Hyperthyroidism was induced by daily s.c. injection of L-thyroxine (L-T4, 250 µg/kg) for 21 days.Results: Hyperthyroidism induced decreased plasma TSH levels and increased plasma free T4 levels (P &lt; 0.001). In addition, it increased plasma oestrogen levels in all cycle phases, and plasma progesterone levels increased in different cycle phases, excluding the oestrus phase, in rats (P &lt; 0.01). By the end of the experiment, ERα percentages were decreased in oestrus days in uterine luminal epithelium; however, ERα percentages were increased in metoestrus phases in hyperthyroid rats. ERα was elevated in proestrus, metoestrus and dioestrus phases in the corpus luteum, and hyperthyroidism also increased ERα percentages in theca folliculi. In uterine luminal epithelium, the hyperthyroidism group showed higher expressions of PgR (P &lt; 0.05) in oestrus and metoestrus phases and decreased oestrus phase compared to control rats.Conclusions: As a result, we conclude that both the levels of plasma estrogen and progesterone as well as the differences in the distributions of relevant receptors in ovarian and uterus tissues have an impact on female infertility due to hyperthyroidism. DOI: http://dx.doi.org/10.3126/ajms.v6i4.11816 Asian Journal of Medical Sciences Vol.6(4) 2015 14-20

Is Dopamine an Iatrogenic Disruptor of Thyroid and Cortisol Function in the Extremely Premature Infant?

Background. Dopamine is frequently used as an inotropic and vasoactive agent in neonatal intensive care units. Recent studies have reported that treatment with dopamine is associated with hypothyroxinaemia of prematurity. Objectives. The aim of this study was to determine if dopamine treatment in extremely premature infants altered thyroid and cortisol function. Methods. We prospectively measured plasma cortisol, TSH, free T4, total T4, and free triiodothyronine concentrations in babies born below 28 weeks’ gestation within 5 days of birth, who were either treated with dopamine (D+) or who did not receive any dopamine (D−) within 12 hours of birth. Clinical Risk Index for Babies scores, lowest mean arterial pressure and highest plasma lactate concentrations in the first 12 hours, were recorded. Results. There were 78 babies included in the study (43 males). Mean gestational age was 25 weeks and 3 days (SD 1.3 weeks). Univariate analyses showed significant differences in cortisol and thyroid function between D+ and D−. Multivariable analyses showed that dopamine, gestation, and CRIB were independent factors affecting FT4 concentrations. No independent factors were shown to affect cortisol or TSH concentrations. Conclusion. Dopamine administration appeared to affect FT4 concentrations but not cortisol concentrations. The mechanisms are unclear but the effect does not appear to be related to hypotension or tissue underperfusion.

Inhibition of angiotensin II increases hypothalamic thyroid hormone and stimulates orexigenic NPY/AgRP neurons (LB437)

We have demonstrated that mice lacking renin (Ren1c ‐/‐) are lean and resistant to diet‐induced obesity, which is associated with increased energy expenditure and uncoupling proteins (UCPs) expression. Surprisingly, plasma catecholamine levels of Ren1c‐/‐ mice were similar to wild type (WT) mice, and their plasma total T3 and T4 were lower than those of WT, although they showed no obvious signs of hypothyroidism. We here investigate whether mice lacking renin display true hypothyroidism, and if so, the specific mechanism by which they develop it. The Ren1c‐/‐ mice have approximately 50% levels of free T3, freeT4 and TSH in the plasma, as well as reduced TRH expression in the hypothalamus compared to WT. Administration of TRH or angiotensin II (Ang II) both restored plasma TSH and thyroid hormones in the Ren1c‐/‐ mice, while these hormones were not affected by human renin, which stimulates mouse MAP kinases but does not cleave mouse angiotensinogen to Ang I. Moreover, the Ang II receptor blocker losartan decreased TRH, TSH, and thyroid hormones of WT mice to the levels similar to those in mice lacking renin. Furthermore, mice lacking renin and WT mice treated with losartan have significantly increased hypothalamic expression of type 2 deiodinase (Dio2), which converts T4 to the more potent T3, and have increased thyroid hormones in the hypothalamus, which likely inhibits TRH through feedback. Both mice lacking renin and WT mice treated with losartan have 3‐fold higher uncoupling protein‐2 (UCP2), orexigenic neuropeptide Y (NPY) and agouti‐related protein (AgRP), as well as 5‐fold lower anorexigenic proopiomelanocortin (POMC) gene expression in the hypothalamus relative to untreated WT mice. In contrast, Ren1c‐/‐ mice treated with human renin had similar expression levels of these genes. These results suggest that the inhibition of Ang II not of Ang‐independent effects of renin causes hypothyroidism and enhances food intake, which likely decrease energy expenditure. We hypothesize that changes in gene expression of the hypothalamus do not contribute to increased energy expenditure of the Ren1c‐/‐ mice, and that hypothalamic hyperthyroidism feedback inhibits TRH, leading to systemic hypothyroidism. Caution should be paid to hypothyroidism when using high dose of inhibitors of the renin angiotensin system.Grant Funding Source: National Science Council: 102‐2320‐B‐009 ‐002 ‐MY3

Maternal hyperthyroidism increases the prevalence of foregut atresias in fetal rats exposed to adriamycin

Gastrointestinal malformations such as esophageal atresia with tracheoesophageal fistula (EA/TEF) and duodenal atresia (DA) have been reported in infants born to hyperthyroid mothers or with congenital hypothyroidism. The present study aimed to test whether maternal thyroid status during embryonic foregut division has any influence on the prevalence of EA/TEF and DA in an accepted rat model of these malformations. Pregnant rats received either vehicle or 1.75 mg/kg i.p. adriamycin on gestational days 7, 8 and 9. Transient maternal hyper or hypothyroidism was induced by oral administration of levothyroxine (LT4, 50 μg/kg/day) or propylthiouracil (PTU, 2 mg/kg/day), respectively, on days 7 to 12 of gestation. Plasma cholesterol, total T3, free T4 and TSH were measured at gestational days 7, 12, and 21. At the end of gestation, the mothers were sacrificed and embryo-fetal mortality was recorded. Fetuses were dissected to determine the prevalence of esophageal and intestinal atresias. At gestational day 12, mothers treated with LT4 or PTU had hyper or hypothyroid status, respectively; plasma cholesterol levels were similar. In the adriamycin-exposed fetuses from hyperthyroid mothers, the embryonal resorption rate and the prevalence of both EA/TEF and DA were significantly higher than in the other groups; maternal hypothyroidism during the same period did not have significant effect on the prevalence of atresias. Maternal hyperthyroidism during the embryonic window corresponding to foregut cleavage increased the prevalence of both EA/TEF and duodenal atresia in fetal rats exposed to adriamycin. This suggests that maternal thyroid hormone status might be involved in the pathogenesis of foregut atresias and invites further research on this likely clinically relevant issue in humans.

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

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

The α′ subunit of β-conglycinin and the A1–5 subunits of glycinin are not essential for many hypolipidemic actions of dietary soy proteins in rats

This study examined the effects of dietary soy protein (SP) lacking different storage protein subunits and isoflavones (ISF) on the abdominal fat, blood lipids, thyroid hormones, and enzymatic activities in rats. Weanling Sprague-Dawley rats (8 males and 8 females/group) were fed diets containing either 20 % casein without or with supplemental isoflavones or alcohol-washed SP isolate or SP concentrates (SPC) prepared from 6 different soy bean lines for 8 weeks. Feeding of diets containing SPC regardless of their subunit compositions significantly lowered relative liver weights, blood total, free, and LDL cholesterol in both genders (P < 0.05) and also reduced serum free fatty acids (FFA) and abdominal fat in females (P < 0.05) compared to the casein or casein + ISF diets. Dietary SPC significantly elevated the plasma free triiodothyronine (T3) in both genders and total T3 in females compared to the casein diet (P < 0.05). The SPC lacking β-conglycinin α' and either the glycinin A1-3 or A1-5 subunits increased total T3 in males and reduced plasma enzymatic activities of creatine kinase and lactate dehydrogenase compared to casein or casein + ISF diet (P < 0.05). Soy isoflavones were mainly responsible for the hypocholesterolemic effects and increased plasma free T3, whereas reduction in FFA, abdominal fat, liver weight and increased plasma total T3 were the effects of the soy proteins. Neither the α' subunit of β-conglycinin nor the A1-5 subunits of glycinin are essential for the hypolipidemic properties of soy proteins.

Exposure to monocrotophos pesticide causes disruption of the hypothalamic–pituitary–thyroid axis in adult male goldfish (Carassius auratus)

The thyroid hormones (THs) 3,3′,5-triiodo-l-thyronine (T3) and l-thyroxine (T4) exert a wide range of biological effects on physiological processes of fish. To elucidate the thyroid disruption effects of monocrotophos (MCP), an organophosphate pesticide, on male goldfish (Carassius auratus), thyroid follicle histology, plasma total T3 (TT3), total T4 (TT4), free T3 (FT3) and free T4 levels, and the mRNA expression of indices involved in the hypothalamic–pituitary–thyroid axis (HPT axis) were examined following 21-day exposure to 0.01, 0.10 and 1.00mg/L of a 40% MCP-based pesticide. The results showed that MCP exposure induced the hyperplasia and hypertrophy of thyroid follicular epithelium and led to decreased plasma TT3 levels and TT3-to-TT4 ratios, without effect on plasma TT4 levels. Profiles of the changes in the relative abundance of deiodinase (D1, D2 and D3) transcripts were observed in the liver, brain and kidneys, during MCP exposure. An increase in the metabolism of T3, expressed as highly elevated hepatic d1 and d3 mRNA levels, might be associated with the reduction in plasma TT3 levels in both the 0.01 and 0.10mg/L groups, while in the 1.00mg/L MCP group, inhibited hepatic d2 transcripts might have also resulted in decreased TT3 levels by preventing the activation of T4 to T3. As a compensatory response to decreased T3 levels, pituitary thyroid-stimulating hormone β subunit mRNA transcription was up-regulated by the MCP pesticide. Decreases in plasma FT3 levels were also correlated with the modulation of hepatic transthyretin mRNA expression. Overall, the MCP pesticide exhibited thyroid-disrupting effects via interference with the HPT axis at multiple potential sites, resulting in disturbance of TH homeostasis.

Low-Dose Thyroxine Attenuates Autism-Associated Adverse Effects of Fetal Alcohol in Male Offspring's Social Behavior and Hippocampal Gene Expression

Fetal alcohol spectrum disorder (FASD) is characterized by neurodevelopmental anomalies manifesting in cognitive and behavioral deficits in the offspring with diverse severities. Social behavior is affected in FASD, and these deficits overlap with those of autism spectrum disorder (ASD). Identifying some of the molecular characteristics related to ASD in an animal model of FASD could ultimately provide details on the underlying molecular mechanisms of both disorders that could lead to novel treatments. Pregnant Sprague-Dawley rats received the following diets: control (C; ad libitum standard laboratory chow), nutritional control pair-fed (PF), ethanol (EtOH), or an EtOH diet supplemented with 0.3, 1.5, or 7.5mg thyroxine (T4)/l in the diet. Social behavior and memory were tested in the adult offspring. Plasma total T4, free T3 (fT3), and thyroid-stimulating hormone (TSH) levels were measured. Hippocampal expression of Gabrb3, Ube3a, Nr2b, Rasgrf1, and Dio3 were measured by RT-qPCR and protein levels of Mecp2 and Slc25a12 by Western blotting. Adult male offspring of EtOH dams showed elevated fT3 and low TSH levels. Adult male, but not female, offspring of EtOH dams exhibited social behavior and memory deficits. Expression of autism candidates, Gabrb3, Ube3a, Mecp2, and Slc25a12, was significantly increased in the hippocampus of male offspring of EtOH dams. Hippocampal Nr2b and Dio3 were also increased, while Rasgrf1 was decreased in the same population. Peripheral thyroid function, social behavioral deficits, and altered expression of the above genes were normalized by simultaneous administration of 0.3mg/l T4 in the EtOH diet. Our data suggest that social interaction deficits of FASD share molecular mechanism with ASD by showing altered hippocampal expression of several ASD candidate genes. Social interaction deficits as well as the gene expression changes in the offspring of EtOH-consuming dams can be reversed by low dose of thyroid hormone supplementation to the mothers.

Brain derived neurotrophic factor and oxidative stress index in pups with developmental hypothyroidism: Neuroprotective effects of selenium

Thyroid hormones (THs) are crucial for growth and development and particularly brain development. The present study was carried out to investigate the brain derived neurotrophic factor (BDNF) and Oxidative stress index (OSI) in the brain of pups born to dams with methimazole (MMI) induced hypothyroidism. Also, to elucidate the effectiveness of selenium (Se) in ameliorating the brain damaging effects induced by maternal hypothyroidism. Our results reveled that plasma free T3 (FT3), free T4 (FT4), growth hormone (GH) were significantly decreased while plasma thyroid stimulating hormone (TSH) was significantly increased in the pups. BDNF level significantly decreased while OSI significantly increased in both the hippocampus and cerebellum in pups born to hypothyroid dams. Se supplementation significantly alleviated the levels of these parameters. The biochemical modifications were confirmed histologically with the abnormal development of the hippocampus and cerebellum and partial reversal of these effects with Se supplementation. We concluded that reduced hippocampal and cerebellar BDNF levels and increment of oxidative stress during early development may contribute to the adverse neurodevelopmental effects of hypothyroidism during pregnancy. Also, Se is an important neuroprotective element that may be used as a dietary supplement against brain damage induced by hypothyroidism.

In Ovo Effects of Two Organophosphate Flame Retardants—TCPP and TDCPP—on Pipping Success, Development, mRNA Expression, and Thyroid Hormone Levels in Chicken Embryos

Tris(1-chloro-2-propyl) phosphate (TCPP) and tris(1,3-dichloro-2-propyl) phosphate (TDCPP) are organic flame retardants detected in the environment and biota for which avian toxicological data are limited. In this study, domestic chicken eggs were injected with TCPP or TDCPP (maximum dose = 51,600 and 45,000ng/g egg, respectively) to determine dose-dependent effects on pipping success, development, hepatic messenger RNA (mRNA) expression levels of genes associated with xenobiotic metabolism and the thyroid hormone (TH) pathway, and TH levels following 20-22 days of incubation. Neither compound reduced pipping success; however, TCPP significantly delayed pipping at 9240 and 51,600ng/g and reduced tarsus length at 51,600ng/g. TDCPP exposure resulted in significant decreases in head plus bill length, embryo mass, and gallbladder size at 45,000ng/g and reduced plasma free T4 levels at 7640ng/g. Type I deiodinase, liver fatty acid-binding protein, and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by TCPP, whereas TDCPP induced CYP3A37 and CYP2H1. Chemical analysis of egg contents at incubation days 0, 5, 11, 18, and 19 revealed that > 92% of the injected TCPP or TDCPP concentration was detectable up to day 5; however, < 1% was detected by day 19. The observed phenotypic responses to TCPP and TDCPP exposure may be associated with disruption of the TH axis, which is critical for normal growth and development in birds. The effects of TDCPP on the gallbladder indicate that the disturbance of lipid metabolism is a likely mechanism of toxicity.

US findings in euthyroid patients with positive antithyroid autoantibody tests compared to normal and hypothyroid cases

We aimed to compare the ultrasonographic and laboratory parameters of euthyroid patients who have only positive antithyroid autoantibody test results with those of patients with a hypothyroid status of Hashimoto's thyroiditis (HT). Thirty-five patients with newly diagnosed HT, 35 euthyroid patients who have autoantibodies against thyroid peroxidase (TPOAb) and/or thyroglobulin (TgAb), and 40 controls were enrolled in the study. Plasma free T3, free T4, thyroid stimulating hormone, TPOAb, and TgAb levels were obtained retrospectively. For gray-scale ultrasonography, each thyroid gland of all individuals graded with gray-scale grading (GSG), which was determined according to the gland size, parenchymal structure, echogenicity, micronodulation, contour irregularity, and existence of hyperechoic septa. For Doppler analysis, the peak systolic velocity (S), resistive index (RI), and pulsatility index (PI) values were obtained from the superior thyroid artery (STA) and intrathyroidal artery (ITA). The color pixel ratio (CPR), which was computationally evaluated from a power Doppler image of all individuals, was used for quantification of the intrathyroidal vascularity. Although the mean GSG values were higher in the HT and antibody-positive groups than they were in the control group, there was no significant difference between the HT and antibody-positive groups. The three study groups demonstrated no statistically significant difference with regard to the S, RI, or PI variables obtained from the STAs and ITAs. Although the CPR values were highest in the HT group, the difference between the HT and antibody-positive group did not reach statistical significance. The euthyroid antibody-positive group revealed gray-scale and Doppler ultrasonographic findings that were similar to those of the HT group.

Thyroid Function after Subtotal Thyroidectomy in Patients with Graves’ Hyperthyroidism

Background. Subtotal thyroidectomy is a surgical procedure, in which the surgeon leaves a small thyroid remnant in situ to preserve thyroid function, thereby preventing lifelong thyroid hormone supplementation therapy. Aim. To evaluate thyroid function after subtotal thyroidectomy for Graves' hyperthyroidism. Subjects and Methods. We retrospectively reviewed the medical records of all patients (n = 62) who underwent subtotal thyroidectomy for recurrent Graves' hyperthyroidism between 1992 and 2008 in our hospital. Thyroid function was defined according to plasma TSH and free T4 values. Results. Median followup after operation was 54.6 months (range 2.1–204.2 months). Only 6% of patients were euthyroid after surgery. The majority of patients (84%) became hypothyroid, whereas 10% of patients had persistent or recurrent hyperthyroidism. Permanent recurrent laryngeal nerve palsy and permanent hypocalcaemia were noted in 1.6% and 3.2% of patients, respectively. Conclusion. In our series, subtotal thyroidectomy for Graves' hyperthyroidism was associated with a high risk of postoperative hypothyroidism and a smaller, but significant, risk of persistent hyperthyroidism. Our data suggest that subtotal thyroidectomy seems to provide very little advantage over total thyroidectomy in terms of postoperative thyroid function.

Central neuropeptide Y infusion and melanocortin 4 receptor antagonism inhibit thyrotropic function by divergent pathways

Weight loss inhibits thyrotropic function and reduces metabolic rate, thereby contributing to weight regain. Under negative energy balance there is an increase in the hypothalamic expression of both neuropeptide Y (NPY) and agouti related peptide (AgRP), the endogenous antagonist of melanocortin 4 (MC4) receptors. Both NPY and MC4 receptor antagonism reduce thyrotropic function centrally, but it is not known whether these pathways operate by similar or distinct mechanisms. We compared the time-course of effects of acute or chronic intracerebroventricular (ICV) administration of NPY (1.2 nmol acute bolus, or 3.5 nmol/day for 6 days) or the MC4 receptor antagonist HS014 (1.5 nmol bolus, or 4.8 nmol/day) on plasma concentrations of thyroid stimulating hormone (TSH) or free thyroxine (T4) in male rats pair-fed with vehicle-infused controls. These doses equipotently induced hyperphagia in acute studies, reduced latency to feed, and increased white adipose tissue mass after 6 days of infusion. Acute central NPY but not HS014 administration significantly reduced plasma TSH concentrations within 30-60 min and plasma free T4 levels within 90-120 min. These inhibitory effects were sustained for up to 5-6 days of continuous NPY infusion. HS014 induced a transient decrease in plasma free T4 levels that was observed only after 1-2 days of continuous ICV infusion. While both NPY and HS014 significantly increased corticosteronemia within an hour after ICV injection, the effect of NPY was significantly more pronounced and was sustained for up to 4 days of administration. Both NPY and HS014 significantly decreased the brown adipose tissue protein levels of uncoupling protein-3. We conclude that central NPY and MC4 antagonism decrease thyrotropic function via partially distinct mechanisms with different time courses, possibly involving glucocorticoid effects of NPY. MC4 receptor antagonism increases adiposity via pathways independent of increased food intake or changes in circulating concentrations of TSH, free T4 or corticosterone.

Thyroid Function and Oppositional Defiant Disorder: More Than a Coincidence in Prepubertal Boys With Attention-Deficit Hyperactivity Disorder?

Thyroid Function and Oppositional Defiant Disorder: More Than a Coincidence in Prepubertal Boys With Attention-Deficit Hyperactivity Disorder?