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PubMed1975

Evaluation of a kit (Thyrolute) for the combined determination of serum total thyroxine and sequential free thyroxine index using Sephadex G-25 and 125I-thyroxine.

A new kit (Thyrolute, Ames) for the combined determination of serum total thyroxine (T-4) and sequential free thyroxine index (F.T.I.) using Sephadex G-25 and 125-thyroxine was evaluated in 136 patients and normal subjects. The T-4 determination was virtually identical to that used in the Ames Tetralute kit and had a similar accuracy and precision. The sequential F.T.I. was compared with a two-stage F.T.I. The two F.T.I.s showed highly significant correlations in the various groups of patients except euthyroid women with raised thyroxine-binding globulin (TBG) (pregnant or oral contraceptive). The overlap found for the sequential F.T.I. between euthyroid, hypothyroid, and thyrotoxic patients was slightly inferior (9%) to that found with the two-stage F.T.I. (6%), but its diagnostic success rate was higher than that of the serum T-4 determination alone. Serial observations of serum T-4 and sequential F.T.I. were also made on eight patients receiving carbimazole-therapy for hyperthyroidism. The sequential F.T.I. showed complete parallelism with serum T-4 regardless of thyroid status, so that it was of no practical value in these patients. It was concluded that the sequential F.T.I kit would be of most value in the smaller hospital laboratory lacking facilities for the radioimmunoassay of thyroid hormones and thyroid stimulating hormone.

Adolescent↗
PubMed1979

Raised total thyroxine and free thyroxine index but normal free thyroxine. A serum abnormality due to inherited increased affinity of iodothyronines for serum binding protein.

2 people from different families had high levels of serum-thyroxine (T4) and a high free T4 (FT4) index but a normal serum triiodothyronine (T3) and serum-reverse-T3 (rT3). The abnormal serum thyroid hormone profile appeared to be inherited in an autosomal dominant manner. Serum-FT4 in affected relatives was normal. The increases in serum-T4 and FT4 index are explained on the basis of an observed increase in affinity of T4 for thyroxine-binding globulin, thyroxine-binding prealbumin, and albumin. The FT4 index did not reflect the true concentration of circulating free T4 in these cases. Thyroid function in the propositi was normal and the results of T4, T3, and rT3 kinetic studies accorded with increased binding of T4 by serum proteins and normal binding of the other iodo-thyronines. This "euthyroid high total T4, normal T3 syndrome" should be kept in mind during diagnostic evaluation of thyroid function.

Female↗
PubMed1985

Relationship between serum free thyroxine, total thyroxine and thyroxine-binding globulin concentrations in patients with Graves' disease.

Statistical analysis of relationship between free thyroxine (FT4) and thyroxine (T4) in patients with Graves' disease has revealed that serum FT4 values correlated well with serum T4 values at variable thyroid states before and during treatment with anti-thyroid drugs. However, the ratio of FT4 concentration to T4 concentration at hyperthyroid state was more than twice as large as the ratio at euthyroid and hypothyroid states. These findings are considered to denote the elevation of per cent of FT4 to T4 (% FT4) in thyrotoxicosis. Nevertheless, thyroxine-binding globulin (TBG) concentrations in hyperthyroid patients were slightly, but significantly lower by 7.3% than those in normal euthyroid volunteers. These results indicate the minimal contribution of the slight decrease in TBG concentrations to the marked elevation of %FT4 in patients with thyrotoxicosis.

Adolescent↗
PubMed1988

[Behavior of the basal and stimulated serum level of thyroid stimulating hormone and determination of thyroxine, thyroxine- binding capacity and free thyroxine index in females with chronic uremia].

In 11 female patients with chronic uraemia at the age of 20 to 47 years (average age 33.1 years) the basal and the thyrotropin releasing hormone-(TRH-) stimulated thyroid gland stimulating hormone-(SH-) secretion were investigated, in addition to this the parameters of the thyroid gland total thyroxin (T4), thyroxin binding capacity (TBC) as well as the free thyroxin-index (FT4-I). In 2 women the investigations were repeated after kidney transplantation. The determination of TSH and T4 was carried out radioimmunologically, TBC was determined according to the principle of the test tube analysis, whereas FT4-I was established by computation. In 9 of the 11 female patients with chronic uraemia a physiological TSH-response behaviour is existing, whereas for T4 deviations from the reference area are to be stated in 7 female patients and for FT4-I in 6 female patients.

Adult↗
PubMed1982

Thyrotropin, total thyroxine, thyroxine binding capacity and free thyroxine index in patients with gonadal dysgenesis (karyotype 45/XO).

In 9 patients with gonadal dysgenesis (karyotype 45/XO), the responsiveness of thyreotropic cells of the pituitary was investigated by stimulation with thyreotropin-releasing hormone (TRH). Both after hormone substitution in the form of sequential therapy (mestranol/mestranol-chlormadinone acetate) and after the end of therapy the investigations were repeated. TSH was determined by RIA, total thyroxine and binding capacity of thyroxine binding globuline (TBC-index) by protein binding assay. The free thyroxine index (FT4-index) was calculated. The results show that the hypothalamic-pituitary unit in patients with gonadal dysgenesis reacts in a similar manner as in normal female subjects.

Adolescent↗
PubMed1981

Serum thyroxine, triiodothyronine, reverse triiodothyronine, thyroid stimulating hormone, thyroxine binding globulin and thyroxine binding pre-albumin concentrations in healthy African adults.

A study of the serum concentrations of the thyroid hormones thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3), thyrotropin (TSH) and the thyroid hormone binding proteins (thyroxine binding globulin (TBG), and thyroxine binding pre-albumin (TBPA)) in non-hospitalized adult Nigerian African subjects was conducted. The subjects were divided into three subgroups, male subjects, non-pregnant female subjects and pregnant female subjects to highlight peculiarities of each sub-group. All three subgroups showed elevation of TBG concentration as compared to British subjects. A statistically significant difference was observed in the concentrations of T4, T3, and TBG in the pregnant female subjects compared to the male and the non-pregnant subjects. A statistically significant difference was also observed between the concentrations rT3 in the male and pregnant female subjects compared to the non-pregnant female subjects. No statistically significant difference was observed between the concentrations of TSH, and TBPA, in all three subgroups, although the mean values for TSH were highest in the pregnant female subjects and the mean values for TBPA and albumin were lowest in this same group. The significance of these findings are discussed in relation to the evaluation of thyroid function in the adult African subject.

Adolescent↗
PubMed1990

Effect of stripping thyroxin from thyroxin-binding globulin on the measurement of free thyroxin in serum by equilibrium dialysis and by radioimmunoassay.

In considering factors that might influence measurement of free thyroxin (T4), we evaluated the proportion (%) of T4 that could be stripped from thyroxin-binding globulin (TBG). The percentage of free T4 was measured in serially diluted sera from four normal subjects, four patients with hyperthyroidism or hypothyroidism, four pregnant women, and four malnourished subjects with low TBG. The critical percentage of stripping was determined by the product of the percentage free T4 and the critical dilution factor (the point where the percentage free T4 began to decrease). The mean values obtained for the respective patient groups--6.38%, 2.76%, 16.73%, 9.75%, and 4.28%--were proved to be related to the rate of saturation of TBG with T4. Values for percentage stripping determined with the "GammaCoat two-step RIA" and the "LiquiSol RIA" were well within the critical percentage stripping by equilibrium dialysis, except in the case of low-TBG serum as measured by LiquiSol RIA. Free T4 concentration as measured by LiquiSol RIA decreased as sample volume decreased. These findings were ascribed to the relatively high values for percentage stripping in the LiquiSol RIA, which led to erroneously low values for free T4.

Adult↗
PubMed1974

Relative rates of transcapillary movement of free thyroxine, protein-bound thyroxine, thyroxine-binding proteins, and albumin.

The rate of appearance of labeled thyroxine (T4) and albumin in lymph from various areas after simultaneous i.v. injection of the labeled substances in conscious ambulatory sheep has been used to estimate the relative rates of transcapillary movement of stable T4 and albumin. Labeled T4 appeared in hepatic lymph at the same rate as albumin. In intestinal and leg lymph, labeled T4 appeared eight and four times as rapidly as albumin indicating that T4 crosses capillaries in these areas independently of and much more rapidly than albumin and other proteins having similar distribution kinetics. The lymph:plasma ratios for all the T4-binding proteins including albumin were very similar in any one area showing that the relative fractional rates of transcapillary movement of these proteins were very similar. Therefore in extrahepatic areas, transcapillary movement of T4 in the protein-bound form was quantitatively much less important than in the free form. The findings support earlier views, recently questioned, that free T4 is of considerable physiological significance.

Animals↗
PubMed1981

[Determination of serum free thyroxine: normal range, relation to the free thyroxine ratio and total thyroxine (author's transl)].

The validity of a commercially available f-T4 radioimmunoassay was investigated in 122 patients with different thyroid status. The normal range of f-T4 was 0.60-2.20 ng/dl in euthyroid patients from an endemic goiter area. No significant difference was found between normals and a group taking oral contraceptives (mean = 1.37 ng/dl vs. 1.45 nd/dl). In patients on thyroid hormone or antithyroid drug therapy, f-T4-values showed a better correlation with the results of an oral TRH-test than total T4 or the free thyroxine ratio (ETR). Specificity of ETR was better than that of f-T4. Sensitivity of f-T4 was higher in the group with negative TRH-test, but lower in hypothyroidism as compared to ETR. Determination of f-T4 by radioimmunoassay is a simple diagnostic procedure. Since f-T4 RIA is not influenced by changes in TBG-levels its use is particularly recommended in cases where such changes are to be expected such as estrogen application or gravidity.

Antithyroid Agents↗
PubMed1972

Active secretion of thyroxine into bile: the role of tissue thyroxine-binding sites.

1. An investigation has been made into factors regulating the secretion of thyroid hormones into bile. The preparation employed was the isolated rat liver perfused with a modified Tyrode solution.2. Tracer amounts of radioactive thyroxine were injected into the Tyrode solution just before its entry into the liver. This allowed the thyroxine-binding sites in the tissue to capture most of the injected hormone. It was found that this tissue-bound hormone was then gradually secreted into the bile and that the process could be resolved into two components. There was a steady, continuous secretion of hormone, which maintained a fairly constant bile:liver ratio in thyroxine concentration of about 2.3. There was also, superimposed upon this, an extra transient secretion of thyroxine occurring just after the injection. This transient effect was abolished by injecting the hormone at 22 degrees C and it was probably due to the sudden flood of free thyroxine into the tissue during the 15 sec injection period.3. Very similar results were obtained with tri-iodothyronine except that the secretion process maintained a higher bile:liver ratio of about 3.7.4. The secretion mechanism was extremely sensitive to changes in temperature and it was able to generate very high concentrations of free thyroxine in the bile. It was concluded that the over-all process was probably an active one.5. The presence of 30% bovine serum in the perfusion fluid did not reduce the bile:liver thyroxine ratio even though it caused a massive fall in the amount of thyroxine in the tissue.6. These results show that the rate of thyroxine secretion into bile is determined by the total amount of thyroxine trapped in the tissue. It is not directly related to the concentration of free thyroxine in the perfusing medium.7. It is suggested that the secretion mechanism works from a small intracellular pool of free thyroxine which is in rapid exchange with the large pool of tissue-bound hormone, and that thyroxine exchange between this small intracellular pool and the free thyroxine pool in the plasma is relatively slow.

Animals↗
PubMed1967

Estimation of rapidly exchangeable cellular thyroxine from the plasma disappearance curves of simultaneously administered thyroxine-131-I and albumin-125-I.

A mathematical analysis of the plasma disappearance curves of simultaneously injected thyroxine-(131)I and albumin-(125)I allows the development of simple formulas for estimating the pool size and transfer kinetics of rapidly exchangeable intracellular thyroxine in man. Evidence is presented that the early distribution kinetics of albumin-(125)I can be used to represent the expansion of the thyroxine-(131)I-plasma protein complex into the extracellular compartment. Calculations indicate that approximately 37% of total body extrathyroidal thyroxine is within such exchangeable tissue stores. The average cellular clearance of thyroxine is 42.7 ml per minute, a value far in excess of the metabolic clearance of this hormone. Results of external measurements over the hepatic area and studies involving hepatic biopsies indicate that the liver is an important but probably not the exclusive component of the intracellular compartment. The partition of thyroxine between cellular and extracellular compartments is determined by the balance of tissue and plasma protein binding factors. The fractional transfer constants are inversely related to the strength of binding of each compartment and directly proportional to the permeability characteristic of the hypothetical membrane separating compartments. Appropriate numerical values for these factors are assigned. An increased fractional entrance of thyroxine-(131)I into the cellular compartment was noted in a patient with congenital decrease in the maximal binding capacity of thyroxine-binding globulin and in three patients after the infusion of 5,5-diphenylhydantoin. Decreased intracellular space and impaired permeability characteristics were observed in five patients with hepatic disease. Studies of the rate of entrance of thyroxine-(131)I and albumin-(125)I into the pleural effusion of a patient with congestive heart failure suggested that transcapillary passage of thyroxine independent of its binding protein is not a predominant factor in the total distribution kinetics of thyroxine-(131)I. The thesis is advanced that the distribution of thyroxine, both within the extracellular compartment and between the extracellular and intracellular compartments, is accomplished largely by the carrier protein and the direct transfer of thyroxine from one binding site to another. The concept of free thyroxine is reassessed in terms of this formulation.

Heart Failure↗
PubMed1982

Inhibition of insulin secretion by L-thyroxine and D-thyroxine treatment in rats under the influence of drugs affecting the adrenergic nervous system.

Both L-thyroxine and D-thyroxine induced an inhibition of glucose-induced insulin secretion with comparable time- and dose-dependent characteristics. L-thyroxine was ten times more potent than D-thyroxine. While L-thyroxine and a ten times higher dose of D-thyroxine had a similar potency in inducing hyperthermia and hypocholesterolaemia, hyperglycaemia in response to D-thyroxine was less pronounced than in response to L-thyroxine. This difference may be explained by a greater depletion of liver glycogen stores and consequently more limited capacity for provision of glucose for the circulation. The results support the view that the differences between L-thyroxine and D-thyroxine are quantitative. Adrenergic contribution to L-thyroxine- and D-thyroxine-induced inhibition of insulin secretion by rat pancreas is apparently of minor importance. Treatment of the rats with propranolol as well as with reserpine or 6-hydroxydopamine did not alleviate L-thyroxine- or D-thyroxine-induced inhibition of insulin secretion by rat pancreas.

Animals↗
PubMed1999

Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism.

BACKGROUND: Patients with hypothyroidism are usually treated with thyroxine (levothyroxine) only, although both thyroxine and triiodothyronine are secreted by the normal thyroid gland. Whether thyroid secretion of triiodothyronine is physiologically important is unknown. METHODS: We compared the effects of thyroxine alone with those of thyroxine plus triiodothyronine (liothyronine) in 33 patients with hypothyroidism. Each patient was studied for two five-week periods. During one period, the patient received his or her usual dose of thyroxine. During the other, the patient received a regimen in which 50 microg of the usual dose of thyroxine was replaced by 12.5 microg of triiodothyronine. The order in which each patient received the two treatments was randomized. Biochemical, physiologic, and psychological tests were performed at the end of each treatment period. RESULTS: The patients had lower serum free and total thyroxine concentrations and higher serum total triiodothyronine concentrations after treatment with thyroxine plus triiodothyronine than after thyroxine alone, whereas the serum thyrotropin concentrations were similar after both treatments. Among 17 scores on tests of cognitive performance and assessments of mood, 6 were better or closer to normal after treatment with thyroxine plus triiodothyronine. Similarly, among 15 visual-analogue scales used to indicate mood and physical status, the results for 10 were significantly better after treatment with thyroxine plus triiodothyronine. The pulse rate and serum sex hormone-binding globulin concentrations were slightly higher after treatment with thyroxine plus triiodothyronine, but blood pressure, serum lipid concentrations, and the results of neurophysiologic tests were similar after the two treatments. CONCLUSIONS: In patients with hypothyroidism, partial substitution of triiodothyronine for thyroxine may improve mood and neuropsychological function; this finding suggests a specific effect of the triiodothyronine normally secreted by the thyroid gland.

Adult↗
PubMed1976

Alterations in enzyme and cytochrome profiles of Rana catesbeiana liver organelles during thyroxine-induced metamorphosis. Changes in membrane-localized phosphohydrolases, oxidoreductases, and cytochrome levels in response to in vivo thyroxine administration.

A primary objective of the present study has been to determine the changes which occur in Rana catesbeiana liver organelle membranes during thyroxine-induced metamorphosis. To this end, enzyme and cytochrome profiles were determined for mitochondria, microsomes, and nuclear membrane fractions isolated from livers of R. catesbeiana tadpoles which had been fasted for 6 days at 15 +/- 0.5 degrees and then immersed in thyroxine, 2.6 X 10(-8) M, for periods of up to 12 days at 23.5 +/- 0.4 degrees. The ratio of total succinate-cytochrome c reductase activity in the initial homogenate fraction to the total activity of this mitochondrial "marker" enzyme recovered in the final mitochondrial fraction remained constant, approximately 0.5, throughout the course of thyroxine treatment; however, after a 3- to 4-day latency the mitochondrial protein mass recovered per unit mass of initial homogenate protein was found to increase significantly (approximately 2-fold by Day 10 of thyroxine treatment). A similar increase was also observed in the yield of microsomal, but not nuclear membrane, protein mass as a function of thyroxine treatment. Prolonged thyroxine treatment (12 days) resulted in approximately 50% decreases in tadpole liver homogenate and microsomal NADH-cytochrome c reductase specific activities; in contrast, mitochondrial and nuclear membrane NADH-cytochrome c reductase specific activities were not altered under the same conditions. In addition, homogenate and microsomal NADPH-cytochrome c reductase specific activities were found to have increased significantly after 12 days of thyroxine treatment; however, the specific activity of NADPH-cytochrome c reductase in the mitochondrial fraction was unchanged. It was also observed that thyroxine treatment resulted in increases in homogenate and microsomal glucose-6-phosphatase specific activities, whereas the mitochondrial as well as nuclear membrane glucose-6-phosphatase specific activities remained unchanged. Furthermore, in contrast to homogenate and mitochondrial monoamine oxidase specific activities, which decreased 30 and 40%, respectively, as a consequence of thyroxine treatment (12 days), the succinate-cytochrome c reductase and oligomycin-sensitive Mg2+ ATPase specific activities determined for these fractions increased significantly. In all instances, changes as a result of thyroxine treatment in membrane-localized homogenate or organelle enzyme specific activities were apparent only after a 3- to 4-day initial latent period. The in vitro effects of thyroxine (10(-10) - 10(-5) M) on the membrane-localized enzyme activities examined in this study were either negligible or, as in the case of mitochondrial succinate-cytochrome c reductase and microsomal NADH-cytochrome c reductase, opposite to the changes observed in response to in vivo thyroxine treatment, with the exception of microsomal NADPH-cytochrome c reductase activity which was enhanced approximately 2-fold by 10(-5) M thyroxine...

Animals↗
PubMed1968

Effect of thyroid-suppressive doses of triiodothyronine on thyroxine turnover and on the free thyroxine fraction.

The relationship between free thyroxine concentration and thyroxine turnover was studied during thyroid suppression with triiodothyronine. Although there was some increase in the proportion of serum thyroxine bound to thyroxine-binding globulin, the ratio of ultrafilterable to protein-bound hormone was not significantly affected. The fractional disappearance rate of thyroxine increased from an average control value of 11.47%/day to 14.72%/day. Because of contraction of the thyroxine distribution space the clearance of thyroxine was less markedly affected, increasing from 1.37 to 1.56 liters/day. Since the ratio of thyroxine turnover to free thyroxine concentration, i.e., the free thyroxine clearance, increased proportionately (4.79-5.55 liters x 10(3)/day) we conclude that triiodothyronine stimulates thyroxine clearance by a mechanism that is independent of effects on free thyroxine concentration.

Blood Protein Electrophoresis↗
PubMed1983

Clinical evaluation of free thyroxine calculation from thyroxine and thyroxine binding globulin radioimmunoassays.

Free T4 calculation was performed based on the equation of the law of mass action between T4 and TBG assessed by routine radioimmunoassay. To examine the validity of this calculation, sera from normal subjects, from hypo- and hyperthyroid patients, from subjects with hereditary deficiency or increase in TBG, and those from uncomplicated pregnancy were included in the assay and the results were compared with those directly measured by radioimmunoassay with encapsulated antibody. Free T4 calculation on the sera described above was almost equal to the free T4 concentration measured directly and reflected clinical thyroid states. Thus, the proposed equation for the calculation of free T4 from total T4 and TBG radioimmunoassay is useful for clinical purposes as well as direct free T4 radioimmunoassay.

Female↗
PubMedDate not supplied

[Reference values for the concentration of free triiodothyronine (FT3), triiodothyronine (TT3), free thyroxine (FT4), thyroxine (TT4), thyrotropin (TSH) and thyroxine-binding globulin (TBG) in umbilical cord blood. Method: luminescence-enhanced enzyme immunoassay].

Physiological concentrations of FT3, TT3, FT4, TT4, TSH and TBG were determined using the luminescence enhanced enzyme immunoassay method in cord blood serum (n = 100). The results are presented in Table 1.

Fetal Blood↗