Decreased Serum T4 Concentrations Research Articles

Cardiovascular problems in rabbits in reference to hypothyroidism - a four-year retrospective study.

The effects of T4 are mainly manifested by positive ino- and chronotropism. The syndrome accompanying hypothyroidism in rabbits (impaired myocardial contractility and reduced ejection capacity) is caused by a deficiency of thyroid hormones - especially T4. The study group consisted of a total of 41 animals: 15 males and 26 females, ranging in age from 2 months to 8 years, with echocardiogram showing reduced fractional shortening (<30%), with normal results of heamatological and biochemical tests. Blood was collected in order to measure T4 level. Echocardiographic examinations were performed with two-dimensional (2D) imaging, M-mode measurements and the pulsed/colour-labelled Doppler technique. Statistical analysis was performed using Statistica 13.0. Correlations were determined: between serum thyroxine concentration and the value of the fraction of shortening in the groups: young animals (up to 5 years of age) and older animals, females and males, and sterilised and non-sterilised animals. Statistical analysis showed a positive correlation between T4 levels in the blood of the test animals and myocardial fractional shortening and heart rate and left-atrial to aortic ratio (LA/Ao) in the pre-treatment period. A positive correlation was also shown after dividing the patients into 2 groups based on their age (below 5 years vs. 5 years and over), sex (male and female rabbits) and fact of sterilization (yes/no). Our study unequivocally confirmed a positive correlation between the decreased serum T4 concentration and reduced fractional shortening, indicating decreased cardiac systolic function in hypothyroid rabbits.

Interaction study with rats given two flame retardants: polybrominated diphenyl ethers (Bromkal 70‐5 DE) and chlorinated paraffins (Cereclor 70L)

AbstractThis study explored possible interaction effects on animal liver microsomal enzymes and thyroid hormones of two flame retardants: Bromkal 70‐5 DE, a mixture of polybrominated diphenyl ethers (hereafter called PBDE); and Cereclor 70L, a mixture of chlorinated paraffins (hereafter called CP).Female Sprague‐Dawley rats were exposed to these compounds in dose ranges of 1.3–18.7 mg/kg bw/day (PBDE) and 1–55 mg/kg bw/day (CP), by gavage for 14 days. Biological responses were measured on liver somatic index (LSI) and hepatic enzyme activity of (a) ethoxyresorufin‐O‐deethylase (EROD) (indicating CYP1A1 activity), (b) pentoxyresorufin‐O‐depentylase (PROD) (indicating CYP2B activity) and (c) the phase II conjugation enzyme uridine diphosphoglucuronosyl transferase (UDP‐GT). The levels of total and free thyroxine hormone in rat plasma (TT4 and FT4, respectively) were also measured. In the experimental work, a Doehlert uniform shell design was used in order to select the combination of concentrations of PBDE and CP administered to the rats. Eight different combinations were used, including a control. The measured responses were modelled with multiple linear regression (MLR), giving response surface plots. The results showed strong synergism between the two flame retardants at one particular exposure combination, resulting in increased hepatic microsomal enzyme responses and decreased serum T4 concentrations. Notably, the exposure combination causing the most marked effects represented intermediate doses of both substances. The mechanisms behind the observed effects are unknown, but may involve induction or inhibition of enzyme systems. Copyright © 2010 John Wiley &amp; Sons, Ltd.

Changes in serum thyroxine and thyroid‐stimulating hormone concentrations in epileptic dogs receiving phenobarbital for one year

A multicentric prospective study was conducted to monitor the effect of phenobarbital on serum total thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations in epileptic dogs. Serum T4 concentrations were determined for 22 epileptic dogs prior to initiation of phenobarbital therapy (time 0), and 3 weeks, 6 months, and 12 months after the start of phenobarbital. Median T4 concentration was significantly lower at 3 weeks and 6 months compared to time 0. Thirty-two percent of dogs had T4 concentrations below the reference range at 6 and 12 months. Nineteen of the 22 dogs had serum TSH concentrations determined at all sampling times. A significant upward trend in median TSH concentration was found. No associations were found between T4 concentration, dose of phenobarbital, or serum phenobarbital concentration. No signs of overt hypothyroidism were evident in dogs with low T4, with one exception. TSH stimulation tests were performed on six of seven dogs with low T4 concentrations at 12 months, and all but one had normal responses. In conclusion, phenobarbital therapy decreased serum T4 concentration but did not appear to cause clinical signs of hypothyroidism. Serum TSH concentrations and TSH stimulation tests suggest that the hypothalamic-pituitary-thyroid axis is functioning appropriately.

Detection of thyroid toxicants in a tier I screening battery and alterations in thyroid endpoints over 28 days of exposure.

Phenobarbital (PB), a thyroid hormone excretion enhancer, and propylthiouracil (PTU), a thyroid hormone-synthesis inhibitor, have been examined in a Tier I screening battery for detecting endocrine-active compounds (EACs). The Tier I battery incorporates two short-term in vivo tests (5-day ovariectomized female battery and 15-day intact male battery using Sprague-Dawley rats) and an in vitro yeast transactivation system (YTS). In addition to the Tier I battery, thyroid endpoints (serum hormone concentrations, liver and thyroid weights, thyroid histology, and UDP-glucuronyltransferase [UDP-GT] and 5'-deiodinase activities) have been evaluated in a 15-day dietary restriction experiment. The purpose was to assess possible confounding of results due to treatment-related decreases in body weight. Finally, several thyroid-related endpoints (serum hormone concentrations, hepatic UDP-GT activity, thyroid weights, thyroid follicular cell proliferation, and histopathology of the thyroid gland) have been evaluated for their utility in detecting thyroid-modulating effects after 1, 2, or 4 weeks of treatment with PB or PTU. In the female battery, changes in thyroid endpoints following PB administration, were limited to decreased serum tri-iodothyronine (T3) and thyroxine (T4) concentrations. There were no changes in thyroid stimulating hormone (TSH) concentrations or in thyroid gland histology. In the male battery, PB administration increased serum TSH and decreased T3 and T4 concentrations. The most sensitive indicator of PB-induced thyroid effects in the male battery was thyroid histology (pale staining and/or depleted colloid). In the female battery, PTU administration produced increases in TSH concentrations, decreases in T3 and T4 concentrations, and microscopic changes (hypertrophy/hyperplasia, colloid depletion) in the thyroid gland. In the male battery, PTU administration caused thyroid gland hypertrophy/hyperplasia and colloid depletion, and the expected thyroid hormonal alterations (increased TSH, and decreased serum T3 and T4 concentrations). The dietary restriction study demonstrated that possible confounding of the data can occur with the thyroid endpoints when body weight decrements are 15% or greater. In the thyroid time course experiment, PB produced increased UDP-GT activity (at all time points), increased serum TSH (4-week time point), decreased serum T3 (1-and 2-week time points) and T4 (all time points), increased relative thyroid weight (2- and 4-week time points), and increased thyroid follicular cell proliferation (1- and 2-week time points). Histological effects in PB-treated rats were limited to mild colloid depletion at the 2- and 4-week time points. At all three time points, PTU increased relative thyroid weight, increased serum TSH, decreased serum T3 and T4, increased thyroid follicular cell proliferation, and produced thyroid gland hyperplasia/hypertrophy. Thyroid gland histopathology, coupled with decreased serum T4 concentrations, has been proposed as the most useful criteria for identifying thyroid toxicants. These data suggest that thyroid gland weight, coupled with thyroid hormone analyses and thyroid histology, are the most reliable endpoints for identifying thyroid gland toxicants in a short-duration screening battery. The data further suggest that 2 weeks is the optimal time point for identifying thyroid toxicants based on the 9 endpoints examined. Hence, the 2-week male battery currently being validated as part of this report should be an effective screen for detecting both potent and weak thyroid toxicants.

OCIMUM SANCTUMLEAF EXTRACT IN THE REGULATION OF THYROID FUNCTION IN THE MALE MOUSE

The effects ofOcimum sanctumleaf extract on the changes in the concentrations of serum triiodothyronine (T3), thyroxine (T4) and serum cholesterol; in the activities of hepatic glucose-6-phosphatase (G-6-P), superoxide dismutase (SOD) and catalase (CAT); hepatic lipid peroxidation (LPO) and on the changes in the weight of the sex organs were investigated. While the plant extract at the dose of 0.5 g kg−1body wt. for 15 days significantly decreased serum T4concentrations, hepatic LPO and G-6-P activity, the activities of endogenous antioxidant enzymes, SOD and CAT were increased by the drug. However, no marked changes were observed in serum T3level, T3/T4ratio and in the concentration of serum cholesterol. It appears thatOcimum sanctumleaf extract is antithyroidic as well as antioxidative in nature.

Counteracting the negative effects of rapeseed and rapeseed press cake in pig diets.

Rapeseed and rapeseed press cake were tested in four long-term experiments with a total of ninety-eight pigs. Rapeseed contained 20 and rapeseed press cake 19 mmol glucosinolates/kg DM. The proportion of the tested rapeseed products in feed amounted to 0 (control), 50, 100 and 150 g/kg diet. Moist-heat-treated rapeseed and rapeseed press cake with an extremely low glucosinolate content were also given at 150 g/kg diet. Each dietary rapeseed product level was given with 125 or 250 microgram supplementary I/kg diet. Reduced feed intake and growth retardation were found in groups receiving 150 g rapeseed products/kg diet; in the case of rapeseed the impairments were significant. Rapeseed products > or = 100g/kg diet increased the thyroid weight and decreased the serum thyroxine (T4) concentration. Higher I dosage brought the serum T4 concentration to the level of the control group and retarded thyroid enlargement. Intake of rapeseed products lowered the I content of the thyroid; however, there was no significant difference between groups given 0.9 mmol glucosinolates/kg diet and those receiving three times as much. Degrading glucosinolates by moisture and heat prevented feed intake depression and growth retardation. In the case of treated rapeseed the decreased serum T4 concentration and increased thyroid weight persisted, indicating formation of some antithyroid compounds due to myrosinase (EC 3.2.3.1) activation. A maximal glucosinolate content of 2 mmol/kg diet and additional I application are a prerequisite for using rapeseed products in pig feeding.

Effects of chronic beta-receptor stimulation on sympathetic nervous system activity, energy expenditure, and thyroid hormones.

The effects of hyper- and hypothyroidism on sympathetic nervous system activity and energy expenditure are well recognized. The impact of altered sympathetic nervous system activity on energy expenditure and thyroid hormone metabolism has not been well studied. We investigated the effects of orally administered terbutaline sulfate, a beta 2-receptor agonist (5 mg, three times per day for 2 weeks), on the activity of the sympathetic nervous system, energy expenditure, and thyroid hormone metabolism in six normal men, aged 21-36 yr. The cardiovascular, metabolic, and thermogenic responses to an infusion of the beta-adrenergic agonist isoproterenol were clearly blunted after 2 weeks of treatment with terbutaline sulfate, indicating down-regulation of beta-receptors and/or development of reduced sensitivity. There were no significant changes in the cardiovascular, metabolic, or thermogenic responses to an infusion of the alpha-adrenergic agonist phenylephrine. Basal metabolic rate was significantly increased by the chronic administration of terbutaline sulfate [5.040 +/- 0.167 (+/- SE) vs. 5.421 +/- 0.234 kJ/min; P less than 0.05]. There was a highly significant change in the serum T3 to T4 ratio (19.4 +/- 1.0 vs. 24.4 +/- 1.0; P less than 0.001). This was a result of increased serum T3 concentrations (136 +/- 9 vs. 160 +/- 14 ng/dl; P less than 0.05) and decreased serum T4 concentrations (7.2 +/- 0.8 vs. 6.7 +/- 0.8 micrograms/dl; P = NS). Chronic beta-receptor stimulation with terbutaline sulfate increases the basal metabolic rate and T3 concentrations. These changes occurred despite down-regulation of beta-receptors and/or decreased sensitivity in response to chronic terbutaline administration.

Reversible Hypothyroidism in Growth Hormone-Deficient Children Treated with Human Growth Hormone

Six children with human growth hormone (hGH) deficiency became hypothyroid during the course of their therapy with hGH. This was accompanied by a decreasing growth rate, clinical symptoms of hypothyroidism and decreased serum T4 concentrations. Three of the 6 patients returned to the euthyroid state, both clinically and biochemically, with cessation of hGH therapy, and reinstitution of hGH precipitated hypothyroidism again in 2 of the three. The patients who remained hypothyroid have evidence of multiple pituitary trophic hormone deficiencies while those who reverted to euthyroidism appear to have isolated hGH deficiency. Evaluation of thyroid function while on hGH showed low T4, free T4 and T3 concentrations. The serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) was absent or markedly blunted in 4 of 6 patients while receiving long-term hGH therapy but was normal or exaggerated in all patients when tested before or after only 5 days of hGH therapy. These data indicate that exogenous hGH results in an inhibition of the TSH response to TRH. The mechanism of this inhibition is unclear, but we postulate that it may be mediated by somatostatin secretion in response to pulse doses of hGH.