Serum Thyroxine Binding Research Articles

4-Hydroxy-2,2′,3,4′,5,5′,6-heptachlorobiphenyl-Mediated Decrease in Serum Thyroxine Level in Mice Occurs through Increase in Accumulation of Thyroxine in the Liver

4-Hydroxy-2,2',3,4',5,5',6-heptachlorobiphenyl (4-OH-CB187) was selected as a major hydroxylated polychlorinated biphenyl metabolite detected from serum of wildlife and humans and was examined for its effect on level of serum thyroid hormone in mice. Four days after treatment of C57BL/6 and DBA/2 mice with 4-OH-CB187 (1.0 mg/kg), the serum total thyroxine (T(4)) and free T(4) levels were decreased in both strains of mice. On the other hand, no significant changes in the level and activity of the T(4)-UDP-glucuronosyltransferases, including UGT1a and UGT1a1, by the 4-OH-CB187 treatment were observed in either strain of mice. No 4-OH-CB187-mediated change in level of serum thyroid-stimulating hormone was observed in either strain of mice. Binding levels of [(125)I]T(4) to serum proteins after administration of [(125)I]T(4) were significantly changed in 4-OH-CB187-pretreated mice: a decrease in the level of serum [(125)I]T(4)-transthyretin (TTR) complex and an increase in the binding level of [(125)I]T(4) to serum albumin and thyroxine binding protein in both strains of mice. Clearance from serum of T(4) was promoted by 4-OH-CB187 pretreatment in both C57BL/6 and DBA/2 mice, and the levels of T(4) in several tissues, especially the liver, were increased. In addition, 4-OH-CB187-mediated decreases in serum total T(4) and free T(4) levels were observed in wild-type and TTR-heterozygous mice but not in TTR-deficient mice. The present findings show that 4-OH-CB187 shows a definite ability to decrease serum T(4) level and further indicate that the 4-OH-CB187-induced decrease would occur through increase in accumulation of T(4) in the liver.

The hypothalamic-pituitary-thyroid axis in preterm infants; changes in the first 24 hours of postnatal life.

The purpose of this study was to measure serum T4, free T4, TSH, T3, rT3, T4 sulfate, and thyroxine binding globulin at four time points within the first 24 h of life (cord and 1, 7, and 24 h) in infants between 24 and 34 wk gestation. The infants were subdivided into gestational age groups: 24-27 wk (n = 22); 28-30 wk (n = 26); and 31-34 wk (n = 24). The TSH surge in the first hour of postnatal life was markedly attenuated in infants of 24-27 wk gestation [8 compared with 20 (28-30 wk) and 23 mU/liter (31-34 wk)]. T4 levels in the most immature group declined over the first 24 h, whereas levels increased in the more mature groups [mean cord and 24-h levels: 65 and 59 (NS) vs. 70 and 84 (P < 0.002) vs. 98 and 125 (NS) nmol/liter]. Free T4 and T3 showed only small, transient increases in the most immature group and progressively larger and sustained increases in the other gestational groups. rT3 and T4 sulfate levels in cord serum were higher in the most immature infants, and in all groups levels decreased initially and then variably increased. The features of a severely attenuated or failed hypothalamic-pituitary-thyroid response to delivery critically define this 24- to 27-wk group as distinct from more mature preterm infants.

Comparative analytical evaluation of thyroid hormone levels in pregnancy and in women taking oral contraceptives: a study from an iodine deficient area

Increase of serum thyroxine binding globulin (TBG) resulting from estrogen action may lead to problems in thyroid diagnostics. The aim of the present study was to define the most diagnostically reliable thyroid parameters in women exposed to differentially elevated estrogens. Sera of three groups of healthy women were analyzed: women taking no medicine (controls), those taking oral contraceptives and pregnant women (in weeks 16 or 32 of gestation). All women involved in the study lived in a moderately iodine-deficient geographical area. Thyroid stimulating hormone (TSH), TBG, total thyroxine (T4), total triiodothyronine (T3) and free T3 were determined and free T4 indices (total T4 × T3 uptake; total T4/thyroxine binding capacity (TBC); total T4/TBG) were calculated. Free T4 was measured simultaneously with a one-step T4-analog enzyme-linked immunosorbent assay (ELISA), a labeled T4 antibody radioimmunoassay (RIA), and a two-step microparticle enzyme immunoassay (MEIA). Estrogen-dependent differences were found in all investigated parameters; however, they remained in the reference interval for TSH, total T4 × T3 uptake, total T4/TBC, free T3 and free T4 MEIA. It was concluded that simultaneous estimations of free T4 and free T3 should follow a primary TSH measurement. The necessity of a distinct reference range has emerged for free thyroid hormones in midterm and late pregnancy as well as in the use of oral contraceptives, especially in iodine-deficient areas.

Serum thyroxine binding capacity-dependent bias in five free thyroxine immunoassays: assessment with serum dilution experiments and impact on diagnostic performance

Objectives: To assess the presence and magnitude of a serum thyroxine binding capacity (sBC)-dependent bias in five free thyroxine (FT 4) immunoassays, compared with equilibrium dialysis (ED). The exhibited bias is confronted with clinical results from previous studies to evaluate its impact on FT 4 determination in sera with various sBC. Design and methods: The sera of three pregnant women and three non thyroidal ill (NTI) patients were serially diluted in an inert buffer to progressively decrease the sBC. FT 4 values were measured in diluted and undiluted samples with the six assays. Results: As a function of increasing dilution performed on pregnancy sera, except for ED and Vitros ECi FT 4, the other four FT 4 assay results decreased to different degrees, in the following order: two-step GammaCoat RIA< Elecsys< ADVIA:Centaur< Amerlex-MAB RIA. In sera from NTI patients, the decrease was more marked and found at high dilution with the Vitros ECi assay. Data from previous studies showed that FT 4 measured with biased assays were decreased only in samples from very severely NTI patients with low sBC and that FT 4 results in pregnancy sera with high sBC were not significantly biased. Conclusions: The dilution test is a sensitive alarm to assess sBC-dependent bias in FT 4 assays. For all FT4 assays and particularly when a bias is observed, documentation should be sought on the diagnostic performance of the assay and supported by a detailed clinical study including samples with low sBC. Physicians should still be educated about the limitations of FT 4 assays.

Serum Thyroxine Binding Capacity-Dependent Bias in an Automated Free Thyroxine Assay

The magnitude of serum thyroxine (T4) binding capacity (sBC) dependent bias in the AXSYM free thyroxine (FT4) assay was assessed using two recently described tests. One of the tests uses a direct equilibrium dialysis (ED) FT4 assay as the reference method. the results obtained with the AXSYM method were compared with those obtained by the ED FT4 method in patient sera having a wide range of sBC. the other test involves comparison of the FT4 results obtained following dilution of sera by an inert buffer, to theoretically derived FT4 results. As serum dilution causes a predictable decrease in sBC, the demonstration of a negative bias whose magnitude increases in parallel to the dilution, is indicative of an sBC-dependent bias. the AXSYM FT4 assay exhibited a significant sBC-dependent bias. This sBC-dependent bias is likely to have been caused by the presence of significant amounts of T4 binding proteins in the assay reagents.

Maternal thyroid function: interpretation of thyroid function tests in pregnancy.

Thyroid status is frequently assessed during pregnancy, both to evaluate suspected thyroid abnormalities, and to monitor the status, of pre-existing thyroid disease. However, the production, circulation, and disposal of thyroid hormone are all altered in pregnancy. Interpretation of thyroid function studies in the pregnant patient must be performed based on an understanding of the normal physiologic changes at each stage of pregnancy. Examples of pregnancy-associated changes include, estrogen-stimulated increase in serum thyroxine binding globulin, chorionic gonadotropin stimulated T4 and T3 production from the thyroid gland, and accelerated degradation of thyroid hormone by the placenta. The serum-TSH alone is usually not adequate to assess thyroid status in pregnancy, and the various conditions that can effect this measurement are described. The pattern of thyroid studies in pregnancy is important in diagnosing thyroid disease, and it may indicate physiologic adaptations to optimize maternal thyroid status for fetal development.

Thyroid function and serum thyroid binding proteins in prepubertal and pubertal children with chronic renal insufficiency receiving conservative treatment, undergoing hemodialysis, or receiving care after renal transplantation

OBJECTIVE: The abnormalities reported in some thyroid function tests in children with renal disease could be adaptive phenomena, shared by a variety of other nonthyroidal illnesses, or could reflect hypothyroidism. STUDY DESIGN: To answer this question, we studied thyroid function and serum thyroid binding proteins in 36 prepubertal and 23 pubertal patients with renal disease receiving three different therapies: conservative treatment, hemodialysis, and care after renal transplantation. RESULTS: During prepuberty, the serum concentration thyroxine binding globulin (mean ± SE) in the three groups of patients (294 ± 18, 303 ± 18, and 323 ± 16 nmol/L, respectively) was significantly lower than in prepubertal control subjects (451 ± 71 nmol/L). Only in prepubertal patients after renal transplantation (3583 ± 573 nmol/L) were serum thyroxine binding prealbumin values lower than in respective control subjects (5999 ± 908 nmol/L). The serum total thyroxine concentration in the three groups of patients (108 ± 41.9, 121 ± 5.7, and 123 ± 5.5 nmol/L, respectively) was significantly lower than in prepubertal control subjects (149 ± 10 nmol/L), whereas serum free thyroxine and serum albumin-bound thyroxine concentrations were similar to those in control subjects. The serum total triiodothyronine level in the three groups of patients (2.29 ± 0.82, 2.13 ± 0.13, and 2.01 ± 0.20 nmol/L, respectively) was significantly lower than in prepubertal control subjects (3.04 ± 0.24 nmol/L), whereas serum levels of free triiodothyronine and serum albumin-bound triiodothyronine were similar to those in prepubertal control subjects. During puberty, serum thyroxine binding globulin and serum thyroxine binding prealbumin levels in the three groups of patients were not statistically different from those in pubertal control subjects (309 ± 47 and 4950 ± 1230 nmol/L, respectively). Serum levels of total thy roxine, free thyroxine, albumin-bound thyroxine, total triiodothyronine, free triiodothyronine, and albumin-bound triiodothyronine were similar to those in pubertal control subjects except for pubertal patients undergoing hemodialysis. In all clinical groups the basal serum thyrotropin concentration was similar to those in respective control subjects. The frequency of goiter was increased in patients undergoing hemodialysis, probably as a result of iodide washout with dialysis. CONCLUSION: Children and adolescents with chronic renal insufficiency or end-stage renal disease or after renal transplantation do not have a primary abnormality of thyroid function and therefore are not candidates for thyroid hormone treatment. (J P EDIATR 1996;128:784-90)

Endemic goiter in the Jos Plateau region of northern Nigeria.

This study is an endemic goiter survey of 3476 school children in 13 Local Government Councils (LGCs) and 1004 subjects in a whole community of one LGC, Plateau State, Northern Nigeria, to determine the prevalence of goiter as well as to identify some of the etiological agents involved. Results of the survey showed that the disease is highly endemic in the area with prevalence varying in places from 1 to 23% of these subjects. Females showed a markedly higher prevalence of goiter. Analysis of 729 urine samples indicated that iodine excretion ranged from 3.5 to 1.3 microgram/dl (32-154 microgram/g creatinine) and was similar to that in iodine deficient areas in the world, but no relation was observed between the prevalence of goiter and urinary iodine. Urinary thiocyanate levels were less than 0.5 mg/dl, suggesting that the role of the thiocyanate as a goitrogen is not important in the region. Thyroid hormone parameters in village subjects with goiter were similar to those in goiter endemia except serum thyroxine (T4). An interesting result found in village subjects was very high serum thyroxine binding globulin, which leads to an increase in serum T4. This study indicated that Northern Nigeria is an area of endemic goiter. Although some areas in Plateau State are iodine deficient zones, we could not conclude that the etiology of endemic goiter in this area is associated with iodine deficiency. There may be an interplay of multiple factors of etiological importance.

Laboratory results for selected target organs in 138 individuals occupationally exposed to TCDD

Blood specimens for dioxin congener analysis and clinical laboratory studies were recently obtained for 138 employees who had been potentially exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) following a 1953 trichlorophenol autoclave accident. Results for 34 clinical tests were regressed on three exposure measures (current TCDD concentration, log TCDD concentration back-calculated to the time of exposure, and chloracne status). Age, smoking status and body-mass-index were included as additional explanatory factors in the analyses. Positive associations were found between each of the exposure measures and both serum thyroxine (T4) and throxine binding globulin (TBG). Additional exposure-response associations were detected relative to several immune system parameters, erythrocyte sedimentation rate, platelet count and serum alkaline phosphatase. These data will be specifically helpful in interpreting the results of additional morbidity and mortality studies conducted within the same target population.

Effects of prolonged training on serum thyrotropin and thyroid hormones in elite strength athletes.

The response of the pituitary-thyroid system was studied in 11 elite weight lifters before, during and after a strength training period of 1 year. During the overall 1 year training period, no systematic changes were found in the concentrations of serum thyrotropin (TSH), thyroxine (T4), free thyroxine (FT4), tri-iodothyronine (T3) and thyroxine binding globulin (TBG). During the pre-competition training period (weeks 15-18), there was a decreased volume of training which was accompanied by a gradual increase in serum T4, FT4 and T3 concentrations. When the intensity of training increased and volume decreased further before the main competition (weeks 19-20), the changes noted returned to their initial levels. It was concluded that in elite strength athletes, intensive training with one training session per day does not lead to major changes in pituitary-thyroid function, but only to minor physiological responses well within the normal range.

Interactions between Oleic Acid and Drug Competitors Influence Specific Binding of Thyroxine in Serum*

Long chain nonesterified fatty acids and various drugs may share albumin-binding sites in common. We questioned whether serum binding of T4 could be indirectly influenced by displacement of drug competitors from these sites by nonesterified fatty acids. The influence of oleic acid on drug-induced inhibition of [125I]T4 binding was measured by equilibrium dialysis, using undiluted serum in order to avoid dilution-related artefacts. Oleic acid (1 mmol/L) alone did not inhibit serum protein binding of T4, but this concentration augmented the inhibitory effects on T4 binding of diflunisal, mefenamic acid, meclofenamic acid, and aspirin. This effect increased with increasing concentrations of mefenamic acid, meclofenamic acid, and furosemide. The T4-displacing effect of fenclofenac was not augmented by oleic acid. The mechanism of these interactions was studied by examining 1) oleic acid effects on drug binding, and 2) drug effects on oleic acid binding in undiluted serum. Increments in added oleic acid (0.5-2.0 mmol/L) progressively increased the mean unbound fractions of [14C]aspirin, [14C] diflunisal, and [14C]furosemide, but did not displace [14C]fenclofenac. At the relevant total and free drug concentrations, the inhibitory effect of oleic acid on drug binding and its influence on drug-induced displacement of T4 were concordant in the order: meclofenamic acid greater than aspirin greater than mefenamic acid greater than diflunisal greater than furosemide greater than fenclofenac. In contrast, drug-induced increases in the unbound fraction of [14C]oleic acid did not correlate with augmentation of T4 displacement. We conclude that synergistic effects of oleic acid and drugs on T4 binding result from drug displacement by oleic acid, rather than the reverse effect. Hence, substances that increase the unbound concentration of a competitor by displacing it from albumin can increase its T4-displacing potency. Interactions between various ligands may exert a greater hormone-displacing effect than the sum of each alone.

Triiodothyronine Uptake Measurement in Serum by Time-Resolved Fluorescence Immunofluorometry

A solid phase competition-type fluoroimmunoassay for triiodothyronine (T3) uptake in serum is described. In the assay, exogenous free T3 binds to the unoccupied binding sites on serum thyroxine binding proteins while the remaining unbound T3 competes with immobilized T3 for binding to a soluble biotinylated anti-T3 monoclonal antibody. The bound biotinylated antibody is quantitated by the addition of streptavidin labeled with the europium chelator 4,7-bis(chlorosulfophenyl-1,10 phenanthroline-2,9-bicarboxylic acid (BCPDA) in the presence of excess europium. The fluorescence signal of the final complex, which is directly proportional to the number of unoccupied binding sites on thyroxine binding proteins, is then measured on the dried solid-phase with a pulsed-laser time-resolved fluorometer. The assay requires a 10 microliters serum sample and a total incubation time of 90 minutes. The coefficients of variation for within-run and between-run assays ranged from 2.0 to 5.7%. Results obtained by the present method compared well with those determined by two commercial radioimmunoassays (r greater than 0.9).

Protein and energy requirements of children with burn trauma

The Sutherland Formula is widely used in the United Kingdom to determine protein and energy requirements of burned children. Achieving the target of this formula can be difficult because of the high levels of protein and energy intake that are inherent in the Sutherland formula calculation. An alternative formula was devised using new parameters, i.e., normal daily nitrogen requirements, wound nitrogen losses and urinary nitrogen losses, which may more closely match the requirements of children with burns. The aim of the study was to evaluate the new formula and to reappraise the Sutherland Formula using current liquid enteral feeds and feeding methods. The study was randomly controlled in design, the Sutherland Fed (SF) Group received enteral feeds according to the Sutherland Formula and East Grinstead Formula (EGF) Group received enteral feeds according to the new East Grinstead Formula. Subjects entered the study on day zero of burn injury. Burn size, using the method of Lund and Browder, was used, to indicate the percentage of body surface area burned. All nutritional intakes were recorded, nutritional parameters, clinical assessments, wound status, medication, body weight changes, serum and urine analysis were assessed. Nine subjects were recruited into the Sutherland Formula Group, mean age 3 years, (range 1-5 years) mean burn size 19% Body Surface Area (BSA), range 10-40%. Eight subjects were recruited into East Grinstead fed Group, mean age 4 years, range 1-13 years mean burn size 15% BSA, range 10-30%. The Sutherland Formula Group achieved 80% of energy targets and 85% of protein targets. The East Grinstead Group achieved 95% of energy targets and 90% of protein targets. Total serum protein and albumin remained within the normal ranges for both groups. Serum Retinol binding protein and thyroxine binding protein showed an upward trend for both groups. Serum IGF-1 and growth hormone remained within the normal range for both groups. A larger number of patients in Sutherland Formula Group required antibiotics than in East Grinstead Formula Group. The Sutherland Formula Group had a negligible weight change -1.3%, whilst the East Grinstead Formula group had a weight gain +2.4%. An intake of 3g/kg/day protein is adequate to meet the requirements of young burned children, as was supplied by the EGF formula. A target protein intake at 4g/kg/day as provided by the Sutherland Formula is probably too high and did not appear necessary in the group of children studied. Children can be successfully and comfortably sustained on enteral feeding for 1-3 week periods and this mode of feeding can be instigated within hours of injury. Enteral feeding may be the only way to achieve EGF targets due to the rigorous demands of the surgical and clinical management procedures endured by these patients. From this work the researcher concluded that the East Grinstead Formula is appropriate for feeding children with burn trauma from a clinical and practical point of view. This study supports the findings of other studies in burned adults in that early enteral feeding of burned children is beneficial in promoting good nutritional status. In addition the low volume, isotonic, high protein enteral feed, with a protein energy ratio of 2 0 %, used in this study, was tolerated by the children studied. Simplification of the East Grinstead Formula for burned children is: Protein 3g/kg BW/day with a protein energy ratio of 17-20%.

A Case of Pseudo-Bartter's Syndrome Associated with Hypergastrinemia, Thrombocytosis and Increased Serum Thyroxine-Binding Globulin.

A housewife, 40 years of age, was admitted with dysesthesia of the extremities, muscle weakness, and attacks of adynamia and thirst. She had been taking a laxative for more than 20 years. On physical examination, blood pressure was 94/56 mmHg. Laboratory tests revealed thrombocytosis, low serum K and marked increases in both plasma renin activity and serum aldosterone. Serum TBG was increased. Serum gastrin was also markedly increased and could not be enhanced by exogenous secretin. Both angiotensin 11 loading test and noradrenalin loading test failed to increase blood pressure. Ammonium chloride loading to examine the disturbance of urinary acidification was abnormal in the short term test and borderline in the long term test. Following a diagnosis of pseudo-Bartter's syndrome induced by long term intake of laxative and repeated diarrhea, the administration of laxative was interrupted and potassium, indomethacin and spironolactone were administered. However, serum K remained low. Hypergastrinemia, thrombocytosis and a high serum TBG level also persisted, the causes of which remain unknown. This is the first reported case of pseudo-Bartter's syndrome associated with hypergastrinemia, thrombocytosis and increased serum TBG.

Thyroid Function in Epileptic Patients Treated With Carbamazepine

The effects of carbamazepine monotherapy on thyroid function were evaluated in patients with epilepsy. A prospective follow-up of 40 patients with recently diagnosed epilepsy was carried out to evaluate the short-term effects. Thirty-three patients receiving long-term carbamazepine therapy (average duration, 4.2 years) and 34 healthy control subjects were studied. Levels of serum thyroxine, free thyroxine, and thyroxine binding globulin were decreased after both 2 and 12 months of therapy with carbamazepine. Low serum thyroxine and free thyroxine concentrations were also found after long-term monotherapy with carbamazepine. Baseline thyrotropin did not change during carbamazepine therapy, but thyrotropin responses to thyrotropin-releasing hormone rose slightly. No correlation was found between serum carbamazepine and hormone concentrations. The results not only support previous suggestions that carbamazepine induces the hepatic clearance of thyroid hormones but also suggest that carbamazepine may have an inhibitory effect at the hypothalamic level.

Thyroid hormone binding in early pregnancy and the risk of spontaneous abortion

Serum thyroxine (T4), free thyroxine (FT4) and thyroxine binding globulin (TBG) were measured at 6, 8, 10, 12, 14 and 16 weeks menstrual age (MA) in 32 pregnant females, who had been selected for a high risk of spontaneous abortion on account of previous abortion (18 cases) or ovulation induction (14 cases). Eight of these subjects experienced a spontaneous abortion occurring between 8 and 20 weeks. The other women, who carried to term, served as controls. In the abortion group, mean pre-abortion TBG and T4 levels were lower than in the control group from the 6th week on. In spite of this, the way T4 changes with TBG was very similar in both groups. No detectable change or difference with respect to control values were observed for FT4. These observations are taken as evidence against impaired maternal thyroid function playing a role in the unsuccessful outcome of pregnancy. Decreased TBG was detected on the average at 5.2 (range 0–13) weeks before abortion. Diagnostic sensitivity and positive predictive value were estimated as about 70 and 80%, respectively, for the high-risk group, indicating that serum TBG might only play a minor role as a predictor of the outcome of pregnancy.

Relationship of oligosaccharide modification to the cause of serum thyroxine-binding globulin excess.

T4-binding globulin (TBG), a glycoprotein with four N-glycosyl complex oligosaccharide chains, exhibits sialic acid-dependent microheterogeneity on isoelectric focusing (IEF). Increasing the sialic acid content of TBG increases its anodal IEF mobility and decreases its rate of in vivo degradation, a mechanism for the elevation of serum TBG levels in pregnancy. In this study, the structure of oligosaccharides in TBG from subjects with various conditions associated with TBG excess was determined by measuring the proportion that bound to Concanavalin-A (Con-A). Since oligosaccharides with three or more branches (antennae) attached to the trimannosyl core are excluded from binding to Con-A, the percentage of serum TBG not bound to Con-A (% peak A) represented the portion of TBG molecules with three or more antennae in all oligosaccharide chains interacting with Con-A. Peak A contained the most anodal IEF bands, while the Con-A-bound TBG (peak B) contained the cathodal bands. Serum samples from 10 normal men and 10 premenopausal women did not significantly differ in terms of TBG levels, % peak A, or IEF mobility and were combined as a single group (normal). Eight subjects with elevated serum TBG levels due to inherited TBG excess [62.0 +/- 10.1 (+/- SD) mg/L] or 2 receiving 5-fluorouracil treatment (26.2 and 31.3 mg/L) compared to 20 normal (14.7 +/- 3.3 mg/L) had % peak A values and IEF mobility similar to those in normal subjects. On the other hand, high serum TBG levels in 8 women during the third trimester of pregnancy (39.2 +/- 5.3 mg/L), 2 women taking oral contraceptives (25.7 and 27.0 mg/L), and 3 women with acute hepatitis (34.8 +/- 4.8 mg/L) were associated with significant elevations of % peak A values (5.68 +/- 1.73%, 3.31% and 2.41%, and 3.25 +/- 0.78%, respectively) compared to those in normal subjects (1.33 +/- 0.40%), as well as increased anodal mobility on IEF. Treatment of a man for 3 days with ethinyl estradiol produced similar changes. Using data from densitometry measurements of IEF bands of TBG, the degree of anodal shift was quantitated (anodal index). This index correlated with the % peak A (r = 0.92) in all study subjects. We conclude that increased sites for sialylation, resulting from the increased proportions of triantennary oligosaccharide chains, account for the increased anodal mobility of TBG in hyperestrogenemia and hepatitis. Thus, in these two conditions, a reduced TBG degradation rate resulting from oligosaccharide modification is the likely mechanism of increased serum TBG levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Serum thyroid hormones, thyrotropin and thyroxine binding globulin during prolonged strength training.

The effects of progressive strength training for 24 weeks on maximal strength and pituitary-thyroid function were studied in 21 males during the training and during the following detraining period of 12 weeks. Maximal strength increased greatly (p less than 0.001) in the first 20 weeks, followed by a plateau phase in the last 4 weeks of training. Maximal strength decreased greatly (p less than 0.001) during the detraining period. The concentrations of serum total (T4) and free thyroxine (fT4) decreased (p less than 0.05 and less than 0.01, respectively) during the training period and they rose to pretraining levels during the detraining period. During the most intense training phase (the last 4 weeks) there was a positive correlation between the changes in serum fT4 concentrations and the changes in maximal force (r = 0.56; p less than 0.01). No statistically significant changes occurred in the levels of serum triiodothyronine, thyrotropin or thyroxine binding globulin. The results show that prolonged intensified strength training can slightly decrease the concentrations of serum total and free T4. These small changes cannot have any clinical significance, and even their physiological significance may be only marginal.

The effect of serum free fatty acid on serum free thyroid hormone fractions in low T3 syndrome

We studied the role of serum free fatty acid (FFA) in the elevation of serum dializable fraction of T4 (DFT4) and evaluated the serum free T4 (FT4) level in low T3 syndrome. Serum DFT4 and DFT3 were measured by equilibrium dialysis method with phosphate buffer, and serum FFA concentration was obtained by gas chromatography. In patients with nonthyroidal systemic illnesses who showed reduced serum total T3 (TT3) and normal total T4 (TT4) (low T3 group, TT3 48 +/- 14 ng/dl, n = 10), mean (+/- SD) DFT4 value (0.032 +/- 0.05%) was significantly higher than that of the group of systemic illnesses with normal TT3 and TT4 (normal T3 group, TT3 79 +/- 7 ng/dl, n = 10). Mean TT4 value of low T3 group (6.5 +/- 1.0 micrograms/dl) was lower than that of normal T3 group (8.6 +/- 2.4 microgram/dl, p less than 0.02). There was no difference in mean absolute FT4 (AFT4) value between the two groups (2.07 +/- 0.46 vs 2.19 +/- 0.53 ng/dl). On the other hand, there was no significant difference in DFT3 value between the groups (0.274 +/- 0.043 vs 0.247 +/- 0.035%), and mean AFT3 of low T3 group (1.29 +/- 0.39 pg/ml) was low than that of normal T3 group (1.92 +/- 0.26 pg/ml, p less than 0.01). In cases of low and normal T3 groups (n = 20), serum thyroxine binding globulin (TBG) concentration had a negative correlation with DFT3 (r = -0.707, p less than 0.001), but not with DFT4. Although there were no significant differences in serum albumin and TBG concentrations between the two groups, the mean serum total FFA concentration and molar ratio of FFA to albumin in low T3 group (579 +/- 249 microM and 1.31 +/- 0.61) were significantly higher than those in normal T3 group (345 +/- 170 microM and 0.75 +/- 0.32, p less than 0.05 and less than 0.025, respectively). All of FFA concentrations in low T3 group, especially oleate, were higher than those in normal T3 group. Moreover, the higher the total FFA concentration was, the greater was the percent fraction of oleate. DFT4 values were significantly increased by the addition of 1 mM oleate to the sera of low T3 group, and this effect was more marked in the sera of the patients with lower albumin concentration.(ABSTRACT TRUNCATED AT 400 WORDS)

Changes in plasma fibronectin levels in patients with thyroid disease and its mechanism

Plasma fibronectin (FN) level was determined in normal subjects and patients with thyroid disease by the Laurell method. In vitro effect of triiodothyronine (T3) on FN synthesis by cultured human fetal skin fibroblasts was also studied. Plasma FN level was 32.2 +/- 5.5 mg/dl (mean +/- SD) in normal adults, and no sex difference was observed. The plasma FN concentrations were increased in patients with hyperthyroidism (63.3 +/- 15.2 mg/dl), decreased in patients with hypothyroidism (19.5 +/- 6.5 mg/dl), and in normal range in patients with simple goiter (30.2 +/- 7.0 mg/dl). These FN values have been normalized with a time lag of a short period after their thyroid function became normal. There was a positive correlation between plasma FN concentrations and serum T3 or T4 concentrations, but a inverse correlation between plasma FN concentrations and serum thyroxine binding globulin or cholesterol levels. In vitro studies revealed that the addition of T3 to the incubation medium stimulated FN synthesis by human fetal skin fibroblasts at the concentrations between 10(-8)M and 10(-6)M. These results indicate the usefulness of plasma FN determination in patients with thyroid disease for their management and studying pathophysiology of the disease, and suggest at the fluctuation of plasma FN concentrations in these patients may at least in part due to the effect of thyroid hormone on FN synthesis by the cells.