Thyroxine Kinetics Research Articles

Kinetics of thyroxine (T(4)) and triiodothyronine (T(3)) transport in the isolated rat heart.

The dynamics and kinetics of thyroid hormone transport in the isolated rat heart were examined using the modified unidirectional paired tracer dilution method. The uptake of (125)I-thyroxine ((125)I-T(4)) and (125)I-triiodothyronine ((125)I-T(3)) from the extracellular space into heart cells was measured relative to the extracellular space marker (3)H-mannitol. The thyroid hormone maximal uptake was 54.4 % for (125)I-T(4) and 52.15 % for (125)I-T(3). The thyroid hormone net uptake was 25.69 % for (125)I-T(4) and 25.49 % for (125)I-T(3). Backflux from the intracellular space was 53.17 % for (125)I-T(4) and 61.59 % for (125)I-T(3). In the presence of unlabelled thyroid hormones, (125)I-T(4) and (125)I-T(3) maximal uptakes were reduced from 10.1 to 59.74 % and from 34.6 to 65.3 %, respectively, depending on the concentration of the unlabelled hormone, suggesting a saturable mechanism of the thyroid hormone uptake by the heart cells, with K(m(T4))= 105.46 microM and the maximal rate of (125)I-thyroid hormone flux from the extracellular space to heart cells (V(max(T4))) = 177.84 nM min(-1) for (125)I-T(4) uptake, and K(m(T3)) = 80.0 microM and V(max(T3)) = 118.5 nM min(-1) for (125)I-T(3) uptake. Experimental Physiology (2001) 86.1, 13-18.

Revised T3 Uptake And T4-To-T3 Conversion In Brain And Cerebellum of 10-Day-Old Rats: A Compartment Analysis

The peripheral and cerebral metabolism of thyroid hormones in 10-day-old rats was evaluated by measuring the kinetics of thyroxine (T 4) and 3,5,3'-triiodothyronine (T 3) fluxes. Labeled iodo-compounds were measured in the plasma, cerebellum and brain (without cerebellum) for 24 hours after the intravenous injection of [125 I]T 4 plus [13 I]T 3. Data were interpreted by compartment analysis. T 4 was produced at 8.93 pmol.h –1 and T 3 at 2.26 pmol.h –1 for 22.7 g body weight. The T 4 and T 3 distribution volumes were 4.26 and 22.7 ml, whereas the extra-cellular fluid volume was 9.42 ml. T 4 was therefore considered to be mostly extra-cellular and T 3 mostly intracellular. This was confirmed in the brain and cerebellum, where the extra-cellular fluid (ECF) fraction was 0.021 ml/g organ and the tissue-to-plasma ratio of labeled and endogenous hormones was 0.54–6.54 ml plasma/g tissue for T 3 and 0.048–0.136 ml plasma/g tissue for T 4. The T 3 in the brain and cerebellum was distributed in several pools. The first, representing 11% of the cerebellum and 8% of the brain (without cerebellum) T 3, was quickly exchanged with circulating T 3. The second pool, derived from the local T 4 5'-deiodination, represented 48% of the cerebellum and 94% of the brain (without cerebellum) hormone; a possible third pool (41% of the hormonal content) in the cerebellum appeared to be unlabeled by radioactive T 3, and motionless. The in vivo T 4 to T 3 conversion, as a function of weight, accounted for 21% of cerebellum needs and 43% of brain needs. The rest was provided by T 3 uptake.

Different tissue distribution, elimination, and kinetics of thyroxine and its conformational analog, the synthetic flavonoid EMD 49209 in the rat.

The synthetic flavonoids EMD 23188 and EMD 49209, developed as T4 analogs, displace T4 from transthyretin, and in vitro they inhibit 5'-deiodinase activity. In vivo EMD 21388 causes tissue-specific changes in thyroid hormone metabolism. In tissues that are dependent on T3 locally produced from T4, total T3 was diminished. It was not known whether it was the presence of EMD interfering with 5'-deiodinase type II in tissues or the decreased T4 (substrate) availability that caused the lowered T3. To study whether the flavonoids enter tissues and, if this were the case, whether they enter tissues similarly, [125I]EMD 49209 together with [131I]T4 were injected into female rats and rats pretreated with EMD 21388. Tissues were extracted and submitted to HPLC. [125I]EMD 49209 disappeared quickly from plasma and enters peripheral tissues; peak values were reached after 0.25-0.5 h. Then [125I]EMD 49209 appeared in the intestines (after 6 h 40% of the dose). Tissue uptake of [131I]T4 was very rapid. EMD 21388 pretreatment caused an increase in the excretion of [125I]EMD 49209 into the intestines (40% after 0.25 h). The uptake of [131I]T4 increased, but not high enough to ensure normal tissue T4 concentrations. In the 5'-deiodinase type II-expressing tissues, no [125I]EMD 49209 could be detected. We conclude that the decrease in T3 locally produced from T4 is caused by the shortage of T4 as substrate and not to a direct effect of EMD on the activity of 5'-deiodinases I and II.

Different Tissue Distribution, Elimination, and Kinetics of Thyroxine and Its Conformational Analog, the Synthetic Flavonoid EMD 49209 in the Rat

Different Tissue Distribution, Elimination, and Kinetics of Thyroxine and Its Conformational Analog, the Synthetic Flavonoid EMD 49209 in the Rat

Development-associated changes in thyroxine kinetics in juvenile salmon.

Smoltification is a transformation that occurs in some species of salmon, during which solitary fish in fresh water become schooling fish and migrate to the sea. This process is accompanied by large increases in plasma T4. T4 secretion rate and other parameters of T4 metabolism in juvenile coho salmon were estimated by applying kinetic analyses to measurements of the disappearance of injected T4 radiotracer from plasma. Studies were performed at the beginning (March) and end (May) of the increase in T4 concentration in fresh water and seawater. Early and intensive sampling permitted characterization of a very fast initial component of the T4 disappearance curve when analyses included a zero time datum derived from an independent estimate of plasma volume. The plasma volume, equal to 1.77% of body weight, was obtained by measuring the disappearance of radiolabeled albumin from the plasma in two other groups of animals in fresh water and seawater. There were 3- to 7-fold changes in T4 production, distribution, and metabolism between March and May, whereas environment (fresh water vs. seawater) had relatively minor effects on T4 kinetics. In fresh water, the T4 secretion rate was 4.48 ng/h in March and 1.50 ng/h in May. The total T4 pool size was 37.8 ng in March and 12.2 ng in May. Plasma-tissue T4 fluxes were 3- to 7-fold greater in May. Relatively less T4 was distributed in tissue in May (63% vs. 83%), and T4 spent much less time in tissue in May than in March during each pass through the tissue space (11 min vs. 3.1 h). We propose that the difference in secretion rate and a redistribution of T4 between blood and tissues contribute to both the rise and fall in the plasma T4 concentration between March and May. Changes in T4 kinetics during salmonid smoltification resemble those occurring during amphibian metamorphosis and mammalian gestation and neonatal life, and may reflect an increased requirement and an important role for thyroid hormones during periods of rapid development in vertebrates in general.

Serum reverse triiodothyronine and thyroxine kinetics in patients with chronic renal failure.

Patients with chronic renal failure (CRF) have reduced serum total T3 (TT3) but normal total rT3 (TrT3) concentrations. These findings contrast with those of nonrenal nonthyroidal illnesses and malnutrition where low TT3 levels are associated with elevated TrT3 values. To evaluate the mechanisms for the normal TrT3 concentrations in CRF patients, iv bolus serum kinetic studies of labeled rT3 were carried out in 13 CRF and 8 normal subjects. In addition, T4 kinetics were studied in 7 CRF and 20 normal individuals. The CRF patients had normal or minimally reduced serum albumin [3.8 ± 0.2 (SE) g/dl] and transferrin (281 ± 17 mg/dl) levels and normal relative BW (95 ± 4%) and body mass index (23.0 ± 0.9 kg/m2) values, indicating adequate protein nutritional status. The mean serum TT3 levels were decreased to 62% of the normal mean (P < 0.001). There were significant increases in the mean values of the percent free fraction of rT3 (135% of normal mean, P < 0.001), free rT3 (131%, P < 0.001) and T4 binding glob...

Thyroxine and Triiodothyronine Kinetics and Extrathyroidal Peripheral Conversion Rate of Thyroxine to Triiodothyronine in Healthy Elderly Humans

The influence of age on the kinetics of thyroxine (T4) and triiodothyronine (T3), and on peripheral conversion of T4 to T3, has been studied, comparing a group of euthyroid, healthy, elderly individuals to a group of young individuals. A monocompartment model was adopted for the kinetics of T4, while a bicompartment model was used for T3. No significant difference (p greater than 0.05) could be found in any of the kinetic parameters of T4 between the elderly and young groups. However, the following significant (p less than 0.05) changes were noted for T3: an increased disposition constant in the phase of slow distribution (beta), shortening of the half-life of this phase (T 1/2 beta ), elevation of the central distribution volume Vc and the elimination constant K23, reduction of the K12: K23 ratio, and increased plasma metabolic clearance and hormonal daily turnover. No significant differences (p greater than 0.05) were observed for the percent turnover of T4 converted to T3.

Inhibition of rat hepatic thyroxine 5'-monodeiodinase by propylthiouracil: relation to site of interaction of thyroxine and glutathione.

When rat liver cytosol, dialyzed free of glutathione, was chromatographed on Sephadex G-100 after incubation with 35S-propylthiouracil, 2 peaks of bound radioactivity were observed, 1 of which contained nearly all the thyroxine 5'-monodeiodinase activity in rat liver cytosol. Binding of propylthiouracil to this peak was inhibited by glutathione but not by thyroxine. Approximately 25% of 35S-propylthiouracil initially bound to the thyroxine 5'-monodeiodinating activity peak remained bound after dialysis, precipitation with trichloroacetic acid, and multipe extractions with ethanol, methanol, and chloroform, suggesting that binding was at least in part covalent. Dialysis studies showed that the presumed covalent binding of 35S-propylthiouracil to the thyroxine 5'-monodeiodinase peak could be inhibited by glutathione, dithioerythritol, and unlabelled propylthiouracil but not by oxidized glutathione or thyroxine. Conversely, thyroxine binding was unaffected by thiol compounds. We studied the kinetics of thyroxine 5'-monodeiodination by radioimmunoassay techniques using rat liver homogenates as source of enzyme and observed the dependence of enzymic reaction upon glutathione (Km = 2.4 mM). Propylthiouracil inhibited the reaction and this inhibition could be overcome with increasing glutathione concentrations. We conclude that the thiol-dependent thyroxine 5'-monodeiodinase is inhibited by propylthiouracil through its covalent binding, probably as mixed disulfide, to s site on the enzyme at which glutathione interacts either as a cosubstrate or reducing agent. This binding site is separate from the site at which thyroxine binds.

Familial thyroxine-binding globulin deficiency in a patient with congenital hypothyroidism.

A kindred with deficiency of thyroxine binding globulin (TBG) was presented. The propositus, a 1-year old female also had congenital hypothyroidism with ectopic (sublingual) thyroid. Decrease in TBG-binding capacity (TBG) values ranging from 1.2-10.2 mug/100 ml) was detected in the seven relatives on the maternal side. Of these subject 2 were male and 5 female; the males had the lowest binding capacities. But six members of paternal relatives were entirely normal in this respect. The mode of inheritance of the abnormality in this family was compatible with the presumption of Nikolai et al. and Shishiba et al., indicating that the inheritance was an X-linked semi-dominant trait. The kinetics of thyroxine (T4) was investigated in a case of partial TBG deficiency with congenital hypothroidism (propositus). The half-life of T4 was shortened, turnover rate increased, extrathyroidal organic iodine and degradetion rate of T4 decreased compared to normal values.

Kinetics of thyroxine and triiodothyronine in a case of thyroxine-binding globulin deficiency with hypothyroidism.

Kinetics of T3 and T4 were studied in a case of TBG deficiency with hypothyroidism. Serum total and free T4 of 35-year-old man were 0.6 μg/100ml and 0.54 ng/100ml, respectively. Serum total and free T3 were 18 ng/100ml and 74 pg/100ml, respectively. BMR was -27%. Thyroidal 24-hr uptake of 131I was 7%. Resin-sponge 131I-T3 uptake was 52%. Binding capacity of TBG was O. Binding capacities of TBPA measured by two different methods were 240 and 223 μg/100ml. The half-life of T4 was shortened, the T4 distribution space, turnover rate and clearance rate increased. Extrathyroidal organic iodine pool and degradation rate decreased. The half-life of T3 was slightly shortened, turnover rate, distribution space and clearance rate increased. Extrathyroidal T3 pool and degradation rate decreased. During the treatment with 75 μg/day of l-T3, the patient's complaints disappeared. When administration of l-T3 was switched to 400 μg/day of l-T4, elevated serum T3 remained higher than the preadministration level. His mother and a younger sister had decreased T4-binding capacity of TBG.

Thyroxine kinetics during prolonged estrogen administration.

ABSTRACT The peripheral metabolism of thyroxine (T4) was studied in 13 patients with carcinoma of the prostate receiving estrogen treatment for at least a year, to ascertain whether changes in T4 degradation had occurred. The control group was composed of 8 healthy men of age and weight comparable to that in patients with prostatic carcinoma. In 6 patients with this same disease, short-term paired studies were carried out before and 3 to 6 weeks following estrogen administration. The 13 estrogen-treated patients had a mean daily T4 degradation rate of 80.5 μg, a value significantly lower (p < 0.02) than that in the normal group. The 24-hr thyroidal 131I uptake in the group receiving chronic treatment was similarly decreased as compared to the euthyroid subjects (p < 0.05). None of the patients with prostatic carcinoma evidenced frank clinical manifestations of hypothyroidism. The 6 untreated patients with carcinoma of the prostate had values of T4 degradation similar to those of the normal group. Subseque...

Effect of hydroflumethiazide on the kinetics of thyroxine in the blood

Effect of hydroflumethiazide on the kinetics of thyroxine in the blood

Occult factitial thyrotoxicosis. Thyroxine kinetics and psychological evaluation in three cases.

Three patients are described with clinical and laboratory findings characteristic of thyrotoxicosis factitia but without proof of self-medication. The diagnosis was supported by the demonstration of accelerated thyroxine turnover comparable to that found in a patient with iatrogenic myxedema receiving large doses of thyroxine. Psychological evaluation of these patients is presented. The term "occult" thyrotoxicosis is suggested for this type of factitial disorder.