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PubMed1986

Studies on the effects of L-thyroxine, L-carnitine and an L-thyroxine-L-carnitine combination on dipalmitoyl phosphatidylcholine content and on phosphatidylcholine species composition in fetal rat lungs.

The aim of the present study was to examine the effects of maternal carnitine treatment combined with thyroxine, a hormone influencing both lung maturation and carnitine metabolism. Administration of a carnitine-thyroxine combination to pregnant rats resulted in a significant increase of DPPC content in fetal rat lungs to 8.8 +/- 1.8 mg/g dry weight (mean +/- SD), compared with the control group, the carnitine-treated group, and the thyroxine-treated group [5.4 +/- 1.8 (p less than 0.01), 5.6 +/- 1.5 (p less than 0.01), and 6.6 +/- 1.0 mg/g dry weight, respectively]. The portion of DPPC in the PC species increased significantly from 20.9 +/- 2.1% in the control group and to 27.2 +/- 3.5% (p less than 0.01) in the carnitine-thyroxine combination group. A significant (p less than 0.01) diminution of the palmitoyl-palmitoleyl PC (16:0/16:1-PC) portion in the PC species was found. Maternal carnitine administration resulted in an elevation of the carnitine levels in the fetal lungs to approximately twice those of the controls (p less than 0.01). The combined administration of carnitine and thyroxine resulted in no increase in the total carnitine content but in a significant (p less than 0.01) increase of the short chain acylcarnitine content. The present results demonstrate that carnitine potentiates the effects of thyroxine on DPPC content and support the concept of an interrelationship between carnitine and thyroxine metabolism.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1986

Concentrations of free thyroxine, total thyroxine, and total triiodothyronine in rabbits immunized with human thyroglobulin.

Levels of serum free thyroxine, total triiodothyronine and total thyroxine were measured in two rabbits (TG-1, TG-2) which had been immunized with human thyroglobulin and produced both anti-thyroglobulin and anti-thyroid hormone antibodies. Despite the presence of both anti-triiodothyronine and -thyroxine antibodies, levels of serum free thyroxine in serial sera obtained from a rabbit (TG-1) stayed within normal range up to 249 days after the first immunization, whereas in the other rabbit (TG-2), serum free thyroxine concentrations of serial sera declined after three immunizations and stayed at lower levels than normal range up to 249 days. Extraction of serial sera from both rabbits disclosed the presence of larger amounts of triiodothyronine and thyroxine in immune sera than preimmune sera. From these results, it is concluded that the presence of anti-thyroid hormone antibodies per se can reduce serum level of free thyroxine in rabbits.

Animals↗
PubMed1985

[Determination of the free thyroxine concentration (FT4) in serum using the FT4 fraction and total thyroxine concentration].

A new equilibrium assay for the determination of serum free thyroxine was evaluated in 514 patients. The assay comprises a two-vial-procedure to measure total thyroxine and free thyroxine fraction by use of monoclonal antibodies. Free thyroxine concentrations are calculated from fT4-fraction and total thyroxine concentration readings. In euthyroidism the average free thyroxine fraction (%fT4) was 0.011%, in hyperthyroidism this fraction was elevated, in hypothyroidism it was below normal. In patients with TBG anomalies, TBG values were inversely correlated with fT4 fraction readings. The "euthyroid reference range" of FT4 (SPAC ET) was between 0.70 to 1.78 ng/dl. This euthyroid range of FT4 was determined from TT4 concentrations measured by T4-RIA (SPAC T4 MONO) which were 30% above TT4 values measured by conventional T4-RIA (SPAC T4 POLY; polyclonal antibodies). However, a different euthyroid range of FT4 between 0.55 to 1.30 ng/dl was observed as well as by other investigators when conventional T4-RIA measurements were used for calculation of FT4 values. Our results indicate that calculated FT4 concentration values are highly dependent on the methods used for determination of total thyroxine concentrations. Precision and reproducibility of this two vial equilibrium assay did not meet the requirements mandatory for the application as a clinical routine diagnostic procedure, and its general use for this purpose can as yet not be recommended.

Adult↗
PubMed1996

[Therapy of euthyroid iron deficiency goiter. Effectiveness of a combination of L-thyroxine and 150 micrograms iodine in comparison with mono-L-thyroxine].

BACKGROUND: In terms of the pathomechanism, TSH and intrathyroid iodine deficiency are the interconnecting elements between alimentary iodine deficiency and the growth and genesis of goiter. L-Thyroxine treatment for suppression of hypophyseal TSH production and supplementary iodide have a synergistic effect in reducing the size of goiter. An individual adaptation of the L-Thyroxine dose is necessary for optimal TSH suppression. Excessive suppression of the TSH level prevents uptake of iodine by the thyroid and thus compensation of the intrathyroid iodine deficiency. Combination therapy of an individually adjusted amount of L-Thyroxine with a small, mostly constant amount of iodine is a recognized concept of goiter therapy today. Administration of a combination preparation with an individually adjustable dose of L-Thyroxine and 150 micrograms iodine complies with these recommendations and improves compliance since only one tablet is required. PATIENTS AND METHODS: In the present study, the thyroid iodine supply, efficacy and tolerance of such a combination preparation was tested for the first time in 49 patients with euthyroid iodine deficiency goiter (group A). 45 patients receiving an individual L-Thyroxine therapy served as controls (group B). RESULTS: Supplementation of individually dosable L-Thyroxine with 150 micrograms iodide leads to a markedly raised iodine excretion in the urine (p < 0.005). This is an indirect indication of an improved thyroid iodine supply. Patients of group A showed a greater reduction of the thyroid volume (18.5% as compared to 16.8%, p = n. s.) and a more persistent TSH suppression (lowering by 39% [group A] as compared to a rise of 17% [group B]) in relation to the initial value (p < 0.004). This is attributable to the improved supply of iodine. CONCLUSION: The combination therapy tested was tolerated just as well as the mono-L-Thyroxine treatment with better efficacy.

Adolescent↗
PubMed1978

Vitamin A and thyroxine carrier proteins in chicken plasma: steady-state control of the plasma level of free retinol-binding protein and free thyroxine.

1. The binding parameters of prealbumin-2 with retinol-binding protein and thyroxine (T4) revealed the existence of distinct and multiple sites for both retinol-binding protein and T4. 2. From the analysis of binding parameters of retinol-binding protein with prealbumin-2 it is clear that under steady-state conditions about 99% of the holo-retinol-binding protein remains bound to prealbumin-2. 3. Equilibrium dialysis studies on binding properties of thyroid hormones with prealbumin-2 revealed that it has a single high affinity site and three low affinity sites. 4. The occurrence of three carrier proteins for thyroid hormones, thyroxine-binding globulin, prealbumin-2 and albumin has been demonstrated. However, the chicken thyroxine-binding globulin differs from human thyroxine-binding globulin by being relatively less acidic and occurring at a two-fold lower concentration. But the thyroid hormone binding parameters are comparable. 5. Highly sensitive methods were developed for determination of T4 binding capacities of the various proteins and plasma level of total T4 by fractionation of carrier proteins and further quantitatively employing in electrophoresis and equilibrium dialysis. 6. The thyroxine-binding proteins were found to be of two types, one (viz., thyroxine-binding globulin) of great affinity but of low binding capacity, which mainly acts as reservoir of T4, and another (viz., prealbumin-2) of low affinity but of high binding capacity, which can participate predominantly in the control of the free T4 pool.

Animals↗
PubMed1975

The exchange of thyroxine between plasma and liver: the role of free thyroxine.

An investigation has been made into the exchange of thyroxine between human plasma and the perfused rat liver. A stop-flow method was used to hold plasma within the liver sinusoids for periods up to 20 min. At 20 degrees C it was found that thyroxine present in the sinusoids transferred to the liver at a rate of 5-6%/min; and that thyroxine transferred from the liver to the plasma at a rate of 1%/min. In a second series of experiments, trace amounts of free thyroxine were injected into the stream of plasma just as it entered the tissue; the liver captured 18.5% of this injected hormone. In the discussion it is noted that 29% of the plasma thyroxine dissociates into free solution each minute. If the liver is able to capture 18.5% of this hormone (as the above experiment suggests) then the plasma-to-liver transfer rate would be 5-6%/min, which is the rate actually observed. These observations strongly suggest that the transfer of thyroxine from plasma to liver involves its initial release into the free state followed by trapping by the tissue binding sites.

Animals↗
PubMed1990

Elevated thyroxine and free thyroxine in euthyroid patients: familial dysalbuminemic hyperthyroxinemia.

An eleven year old male was evaluated because of persistent elevation of thyroxine levels and elevated thyroxine index calculated as "T7" but normal thyrotropin levels. The findings were demonstrated by thyroxine binding protein electrophoresis to be due to aberrant thyroxine binding to albumin. The abnormality was also documented in the patient's father. This entity, known as familial dysalbuminemic hyperthyroxinemia, is being reported with increasing frequency and should be suspected when elevated total thyroxine and free thyroxine or "T7" levels are associated with a normal thyrotropin level. The case reported is somewhat unusual in that the triiodothyronine affinity of the aberrant protein appears to be more pronounced than usually reported with this syndrome and the corresponding total triiodothyronine level was significantly elevated.

Child↗
PubMed1989

Thyroxine may decrease serum thyroxine-binding globulin levels.

The purpose of this study was to elucidate the influence of thyroxine on the serum thyroxine-binding globulin (TBG) levels. Serum TBG levels were determined in 100 normal people, 100 cases of simple goiter, 50 cases of nodular goiter, 50 cases of Graves' disease and 70 cases of autoimmune thyroiditis (35 cases in the euthyroid state, and 35 cases in the hypothyroid state). The serum TBG levels were 14.3 +/- 0.3 micrograms/ml (mean +/- SE) in the normal control, 14.1 +/- 0.4 micrograms/ml in simple goiters, 14.9 +/- 0.5 micrograms/ml in nodular goiters, 13.0 +/- 0.5 micrograms/ml in Graves' disease, 15.0 +/- 0.6 micrograms/ml in euthyroid autoimmune thyroiditis and 17.4 +/- 0.8 micrograms/ml in hypothyroid autoimmune thyroiditis. The serum TBG levels were significantly decreased in Graves' disease (p less than 0.05) and significantly increased in hypothyroid autoimmune thyroiditis (p less than or equal to 0.01) as compared with the control. Serum TBG levels were determined after treatment by antithyroid drugs in 25 cases of Graves' disease, by thyroxine replacement therapy in 15 cases of hypothyroid autoimmune thyroiditis and by thyroxine suppression therapy in 25 cases of nodular goiter. Serum TBG levels increased significantly after treatment with antithyroid drugs (p less than 0.005) in Graves' disease. Serum TBG levels decreased significantly both after treatment with thyroxine (p less than 0.01) in hypothyroid autoimmune thyroiditis and after treatment with thyroxine (p less than 0.005) in nodular goiter. This evidence supports the conclusion that T4 may decrease serum concentrations of TBG.

Animals↗
PubMed1985

Comprehensive study of a thyroxin-analog-based assay for free thyroxin ("Amerlex FT4").

The basic theory of thyroxin-analog-based radioimmunoassays for free thyroxin has been extended to evaluate definitively the effects arising from residual binding of the tracer analog to serum proteins. Using experimentally determined binding constants and computer simulation techniques, we studied the effects of thyroxin-analog binding to serum proteins on results of Amerlex FT4 radioimmunoassay, using this improved mathematical model. Results from computer-simulation studies were compared both directly with in vitro experimental results and indirectly with clinical studies. Agreement was good among all three approaches. The relatively weak binding of analog to thyroxin-binding globulin and prealbumin does not significantly perturb Amerlex FT4 assay results. Binding of the analog by albumin has a small but quantifiable effect on assay results, amounting to an intrinsic bias of 0.08 pmol of free thyroxin per liter per gram of albumin per liter for euthyroid serum samples. This bias is unlikely to be important for most clinical laboratory samples, but it may be significant when one is interpreting results for those rare patients with genetic albumin abnormalities such as analbuminemia or familial dysalbuminemic hyperthyroxinemia. Massively increased concentrations of nonesterified fatty acids (e.g., after treatment with heparin) will lead to a spurious increase in free thyroxin in this and most other techniques, including equilibrium dialysis.

Computers↗
PubMed1986

A novel enzyme immunoassay for total thyroxine using immobilized antibodies and hydrophobic chromatography purified thyroxine-peroxidase conjugate.

A new and simple competitive enzyme immunoassay method for the measurement of total thyroxine in serum is described. Anti-thyroxine antibodies, raised in sheep with a bovine serum albumin-thyroxine conjugate prepared with carbodiimide as coupling initiator, were physically adsorbed onto a large surface area polypropylene support. Competition occurred between thyroxine in the sample and a thyroxine-peroxidase conjugate prepared with a glutaraldehyde spacer and further purified by octyl Sepharose hydrophobic chromatography. The entire assay was performed in 2 h with a useful range of 10-300 micrograms/l. The coefficients of variation ranged from 6.9 to 12% and good agreement (r = 0.93-0.97) was found between this method and 2 radioimmunoassays on 71 serum samples having well distributed thyroxine values.

Animals↗
PubMed1984

The preparation and characterization of alkaline phosphatase-thyroxine conjugates and their use in the enzyme immunoassay of thyroxine.

Alkaline phosphatase from calf intestine was conjugated to thyroxine using cyanuric chloride, glutaraldehyde and 1-cyclohexyl-3(-2 morphoinoethyl)-carbodiimide as coupling reagents. The conjugates produced were studied for incorporation of thyroxine, retention of enzyme activity and immunoreactivity in a thyroxine radioimmunoassay system against a range of thyroxine antisera. The use of these conjugates in thyroxine enzyme immunoassay was studied using second-antibody separation. Comparison of the results with radioimmunoassay data was satisfactory and indicates the potential of these conjugates for thyroxine immunoassay. The use of cyanuric chloride as a coupling reagent was unsatisfactory, but good results were obtained with glutaraldehyde. Although satisfactory immunoreactivity of carbodiimide conjugates was observed in a radioimmunoassay system, these results were not reflected in the enzyme immunoassay systems studied.

Alkaline Phosphatase↗
PubMed1987

Free thyroxine, free triiodothyronine, and thyrotropin concentrations in hypothyroid and thyroid carcinoma patients receiving thyroxine therapy.

Free thyroxine (FT4) and free triiodothyronine (FT3) concentrations in serum were measured by direct equilibrium dialysis methods in patients receiving thyroxine replacement or suppression therapy. Four of 50 hypothyroid patients euthyroid on replacement therapy (mean thyroxine dose 120 micrograms/day) had supranormal FT4 concentrations, whereas the FT3 concentrations were normal in all. Forty-one of 56 operated thyroid carcinoma patients on suppressive therapy (mean thyroxine dose 214 micrograms/day) had raised FT4 concentrations, whereas the FT3 concentrations was elevated in only one patient. There was a large difference in mean FT4 values for hypothyroid and thyroid carcinoma patients (17.2 vs 29.5 pmol/l), whereas the difference in mean FT3 values was small (5.0 vs 6.1 pmol/l), suggesting a decreased peripheral conversion of T4 to T3 with increasing concentrations of FT4. Serum TSH concentrations, as determined by an immunoradiometric assay, varied from less than 0.02 to 11.9 mU/l in treated hypothyroid patients; 21 patients (42%) had values outside the reference limits. As a single test, serum TSH is therefore not very useful for the assessment of adequate thyroxine dosage in patients with primary hypothyroidism. In thyroid carcinoma patients, the TSH concentrations were less than 0.18 mU/l; 45 patients had values less than 0.02 mU/l indicating sufficient suppression of TSH secretion in the majority of cases. On the basis of these results we recommend the combination of FT3 and TSH tests for monitoring thyroxine replacement and suppression therapy. FT4 appears less useful than FT3 for this purpose even if special reference values values were adopted for each patient group.

Adult↗
PubMed2005

Total long-term within-laboratory precision of cortisol, ferritin, thyroxine, free thyroxine, and thyroid-stimulating hormone assays based on a College of American Pathologists fresh frozen serum study: do available methods meet medical needs for precision?

CONTEXT: It is important that the total long-term precision of laboratory methods meet the medical needs of the patients being served. OBJECTIVES: To determine the long-term within- and between-laboratory variation of cortisol, ferritin, thyroxine, free thyroxine, and thyroid-stimulating hormone measurements using commonly available methods and to determine if these variations are within accepted medical needs. DESIGN: Two vials of pooled frozen serum were mailed 6 months apart to laboratories participating in 2 separate College of American Pathologists surveys. The data from those laboratories that analyzed an analyte in both surveys were used to determine for each method the total variance and the within- and between-laboratory components. SETTING: The study included the A mailing of the 2003 College of American Pathologists Ligand Survey and the C mailing of the Chemistry Survey. MAIN OUTCOME MEASURES: For each analyte, total variance was partitioned into within- and between-laboratory components for each analytic method. The within-laboratory variations were then compared with imprecision criteria based on biological variation. PARTICIPANTS: The laboratories that reported results on the same analyte using the same method in both surveys. RESULTS: For each analyte, the median of the long-term within-laboratory variances of each peer group was 78% to 95% of its total-survey variance, and the median long-term within-laboratory coefficients of variation varied from 5.1% to 7.6%. The number of methods that met within-laboratory imprecision goals based on biological criteria were 5 of 5 for cortisol; 5 of 7 for ferritin; 0 of 7 for thyroxine and free thyroxine; and 8 of 8 for thyroid-stimulating hormone. CONCLUSIONS: For all analytes tested, the total within-laboratory component of variance was the major source of variability in this study. In addition, there are several methods, especially for thyroxine and free thyroxine, that may not meet analytic goals in terms of their imprecision.

Clinical Laboratory Techniques↗
PubMed1984

Effects of dextro-thyroxine, a preparation almost free of levo-thyroxine, on thyroid function, serum lipids and apolipoprotein A-I in "double pre-beta lipoproteinemia".

Eight subjects, belonging to a large family kindred repeatedly showing the electrophoretic pattern of the "double pre-beta lipoproteinemia", were studied. In seven of them thyroid function, serum lipids and apolipoprotein A-I were determined before and after treatment with dextro-thyroxine, preparation almost free of levo-thyroxine. In most of the patients, total-T4 levels and free-T4 Index were in the lower normal range, but basal TSH levels and the TSH response to TRH were normal. Dextro-thyroxine was effective in reducing both serum total cholesterol and triglycerides, but the percentage decrease in serum triglycerides was definitely greater than that of serum total cholesterol. This marked, unexpected hypotriglyceridemic effect is similar to that observed in a group of obese, hypertriglyceridemic hypothyroid patients treated with levo-thyroxine. Besides serum total cholesterol and triglycerides, the VLDL cholesterol/triglycerides ratio and the electrophoretic "slow moving" pre-beta component were also significantly reduced after treatment, suggesting that dextro-thyroxine can remove efficiently "remnant" VLDL particles from the plasma. Following dextro-thyroxine therapy, the relatively low pretreatment values of apolipoprotein A-I were significantly increased, being restored to normal.

Adult↗
PubMedDate not supplied

[Reference values for blood levels of free thyroxine, free triiodothyronine and thyroxine-binding globulins in euthyroid children. Method: luminescence-enhanced enzyme immunoassay].

Concentrations of free thyroxine (n = 296, male 164, female = 132), free triiodothyronine (n = 273, male 156, female = 117) and thyroxine-binding globulin (n = 273, male 156, female = 117) were determined using the luminescence enhanced enzyme immunoassay method in blood-serum of euthyroid children. Beyond the 30, day of life no significant differences were found in different age groups for the free thyroxine and beyond the 2, day of life for the free triiodothyronine concentration. The free thyroxine values of the infants in the range of 15-39 pg/ml decreased to the range of 9-18.5 pg/ml and the free triiodothyronine values decreased from 3.4-9.3 pg/ml to the range of 2.8-6.5 pg/ml. The values for thyroxine-binding globulin increased in the first month of life up to the range of 18-35 mg/l and decreased afterwards continuously to the range of 14.5-26.5 mg/l.

Adolescent↗
PubMedDate not supplied

[Behavior of the concentration of triiodothyronine, thyroxine, thyrotropin and thyroxine-binding globulin in the serum of children with nephrotic syndrome].

Concentrations of triiodothyronine, thyroxine, thyrotropin, thyroxine-binding globulin, urea, creatinine, cholesterol and total protein were determined in serum of six children (ages from 4 to 16 years) with nephrotic syndrome undergoing therapy. The results showed that with decreasing concentration of serum protein and increasing concentration of cholesterol the concentrations of thyroxine and thyroxine-binding globulin decreased whereas the concentration of thyrotropin was elevated. Improvement in the concentration of serum protein lead to an improvement of serum levels of thyroid hormones and thyroxine-binding globulin; concentrations of thyrotropin and cholesterol returned to values close to normal. Although triiodothyronine was decreased slightly it remained in the normal range thus preventing overt hypothyroidism.

Adolescent↗
PubMed1971

An examination of the extent of reversibility of thyroxine binding within the thyroxine distribution space in the rabbit.

1. New Zealand white rabbits were injected intraperitoneally with [(125)]L-thyroxine. Experiments were performed after 24 hr had elapsed.2. Thyroxine distribution space was calculated as 129 ml. kg(-1). Half-life of disappearance of thyroxine from the blood of the urethane anaesthetized rabbit was 653 min.3. After exchange of approximately 20 ml. kg(-1) whole blood with heparinized blood from a non-radioactive donor, equilibration of radioactivity in the recipient had produced a peak radioactivity by 2 hr.4. The thyroxine space in which complete exchange took place within 2 hr was 102.7 +/- 4.7 ml. kg(-1) in six rabbits. This is 79.6% of the thyroxine distribution space.5. These results are compared with observations in the rat.

Animals↗
PubMed1975

Determination of serum thyroxine after dissociation from thyroxine-binding globulin in alkaline solution and absorption on dextran-coated charcoal.

A competitive protein-binding procedure for determining serum thyroxine is described in which thyroxine is described in which thyroxine is first dissociated from serum thyroxine-binding globulins in an alkaline solution. After binding equilibration, the unbound thyroxine is separated by dextran-coated charcoal. The procedure takes only 100 mul of serum, requires no evaporation, and is sensitive and reproducible. Results by this procedure correlate well with those for a generally accepted method.

Charcoal↗