Serum Thyroxine-binding Globulin Research Articles

Thyroid hormones changes in infants and children with metabolic acidosis

The influence of the acidotic state on the thyroxine (T4) peripheral metabolism was studied in two different forms of metabolic acidosis, ie infantile diarrhea and diabetic ketoacidosis. The serum concentrations of T4, free T4 (FT4), triiodothyronine (T3), reverse T3 (rT3), thyrotropin (TSH) and thyroxine-binding globulin (TBG) were measured and compared to healthy control groups. Lower T4 and T3 and higher rT3 serum concentrations were found in both tested groups of patients in relation to the control groups. In infants with severe metabolic acidosis FT4 values were lower than those observed in the control group. In addition, serum TBG levels were lower in diabetic patients as compared to control subjects. Despite the reduced serum T3 and T4 concentrations in both groups of patients, TSH concentrations, were within the normal range. Therefore, we concluded that acidosis caused either by diarrhea (not so far described) or by diabetes mellitus (well documented up to now) affects the thyroid hormones metabolism in a similar way, at least as far as the thyroid hormones blood levels are concerned.

Impaired binding properties of thyroxine-binding globulin in hepatocellular carcinoma and chronic liver disease.

To determine the factors underlying the apparent reduction in binding ability of thyroxine-binding globulin in hepatocellular carcinoma, hormone-binding characteristics were further examined in patients with this disease and in control subjects. No differences in affinity constants with respect to triodothyronine or serum thyroxine-binding globulin from hepatocellular carcinoma, cirrhotic and normal subjects were found. The affinity for thyroxine was significantly reduced in hepatocellular carcinoma (0.41 +/- 0.13 x 10(10) mol-1) and cirrhotic (0.65 +/- 0.1 x 10(10) mol-1) patients compared with normal subjects (0.94 +/- 0.7 x 10(10) mol-1). Investigations carried out on liver tissue obtained from patients with hepatocellular carcinoma and chronic liver disease showed that thyroxine-binding globulin within tumor tissue was elevated and bound less exogenous tracer hormone compared with that obtained from nontumor tissue. Tumor-derived thyroxine-binding globulin with altered binding properties is, at least partly, responsible for the abnormal behavior of the serum protein in patients with hepatocellular carcinoma.

Dietary Restriction on Serum Thyroid Hormone Levels

To determine the long term effects of a protein sparing fast on serum thyroid hormone levels, the authors studied 38 obese patients ingesting a diet of 320 kcal for up to 13 weeks. The high baseline serum triiodothyronine (T3) levels decreased significantly by the first week, further decreased by the third week, and this lower level persisted for the duration of the fast until realimentation. Serum free T3 index followed the same general pattern as did serum T3 levels. Serum reverse T3 increased significantly by the first week, but by week three, the reverse T3 level had begun to fall, although still significantly increased above baseline. By week seven, reverse T3 had decreased to almost baseline and remained not significantly changed from the baseline to 13 weeks. Serum thyroxine (T4) increased significantly by the first week in all patients, but by the third week had returned to baseline levels which persisted to 13 weeks. The free T4 index and free T4 concentrations showed the same increment at week one and then returned to baseline levels. There were no significant changes in serum thyroxine-binding globulin (TBG) or thyroid-stimulating hormone (TSH) concentrations. The changes in serum T3 and reverse T3 levels are attributable to alterations in peripheral 5'-monodeiodination of T4 and reverse T3 induced by the protein sparing fast.

Thyroxine-binding globulin, hyperthyroxinemia and hepatocellular carcinoma

To determine serum thyroxine-binding globulin (TBG) levels, we used radioimmunoassay, and compared the results obtained with other tests in 231 patients with chronic hepatitis B virus infection to evaluate its clinical implications. All of these patients were hepatitis B surface antigen (HBsAg)-positive. Among them, 38 patients had hepatocellular carcinoma (HCC), 18 had chronic persistent hepatitis, 70 had chronic lobular or active hepatitis (grouped as CAH), 31 had active cirrhosis (AC), 25 had inactive cirrhosis, 20 had decompensated cirrhosis, and 29 were “healthy” HBsAg carriers. Twenty-seven patients with acute hepatitis, 12 with cancer metastasis to the liver, and 81 normal adults served as disease or normal controls. The results showed that serum TBG level increased significantly in patients with CAH, AC, or HCC. Serum TBG did not correlate with albumin or bilirubin level, but correlated with alanine aminotransferase (ALT) positively in patients with CAH (p < 0.001) and negatively in patients with HCC (p < 0.01) (slope difference p < 0.05). Serial determination of serum TBG and ALT also showed parallel changes in 15 patients with CAH, but not in nine patients with HCC. In contrast, the fall and rise of serum TBG levels in patients with HCC coincided with tumor resection and recurrence. The data suggest that serum TBG elevation in patients with hepatitis activity is the result of hepatocellular damage, whereas that in patients with HCC is due to increased synthesis. Whether serum TBG elevation without concomitant rise of ALT could be used as a marker of HCC awaits further study.

Biochemical Thyroid Profile in Patients Infected with the Human Immunodeficiency Virus

Over a 2-year period, thyroid function was studied in 102 patients infected with the human immunodeficiency virus (HIV) and in 102 age- and sex-matched controls with various infectious diseases. Biochemical abnormalities were observed in 1-20% of the patients, depending on thyroid indices, but thyroid disease (hypothyroidism) was diagnosed in only 1. Compared to controls, patients, especially those with the acquired immunodeficiency syndrome (AIDS), had a significant increase in serum thyroxine-binding globulin, a lower T3 and free thyroxine index, and a higher frequency of thyroglobulin antibodies.

Elevation of serum thyroxine-binding globulin (but not of cortisol-binding globulin and sex hormone-binding globulin) associated with the progression of human immunodeficiency virus infection

purpose: In order to assess the relation of thyroid function tests to human immunodeficiency virus (HIV) infection, we determined the levels of serum thyroid hormones, serum binding proteins [thyroxine-binding globulin (TBG), cortisol-binding globulin (CBG), and sex hormone-binding globulin (SHBG)], and serum tumor necrosis factor (TNF) in HIV-seropositive subjects at different clinical stages. patients and methods: Thirty-seven HIV-seropositive patients were studied: 7 at stage II, 13 at stage III, and 17 at stage IV (eight ambulatory and nine hospitalized) according to the Centers for Disease Control's criteria. results: As compared with stage II and stage III patients, stage IV patients had significantly higher mean TBG and total thyroxine (TT 4) values, similar and normal total triiodothyronine (TT 3) levels, and similar and abnormally low reverse triiodothyronine (rT 3) concentrations. However, stage IV hospitalized patients had significantly lower TT 3 values than stage IV ambulatory patients. In contrast to TBG, mean levels of CBG and SHBG were comparable in the three groups and within normal limits. For the whole population of HIV patients, there was a highly significant correlation between the CD 4 lymphocyte count and TBG (r = −0.529, p <0.001) but not with CBG and SHBG levels. Finally, TNF values higher than 10 pg/mL were detected in six of the 17 stage IV patients and in only one of the 13 stage III patients (p = 0.059); elevated TNF levels correlated with a lower CD 4 count (p <0.01) but not with serum TBG levels. conclusion: The progression of HIV infection is associated with an elevation of serum TNF and TBG, but not of CBG or SHBG. HIV-infected patients have an unexpectedly normal TT 3-low rT 3 state.

Immunological quantitation of rat and mouse thyroxine-binding globulins. Ontogenesis and sex-dependence of the circulating levels of the thyroxine-binding globulins

We describe the preparation of monospecific antisera against a thyroxine-binding globulin partially purified from immature rat sera by affinity chromatography on thyroxine-Sepharose. The antisera are used for the rocket immunoelectrophoresis assay of rat thyroxine-binding globulin and also, owing to their partial cross-reactivity with mouse thyroxine-binding globulin, for the quantitation of this serum binding protein in the mouse. The thyroxine-binding globulin is measured in developing rats and in sexually mature male and female rats and mice. The results of the ontogenetic study confirm the postnatal surge of serum thyroxine-binding globulin levels, formerly demonstrated with binding techniques. They allow further to define the correlations, dependent on age, of the immunoquantitated thyroxine-binding globulin and transthyretin levels with the abilities of the sera to bind thyroxine. In sexually mature rats and mice we demonstrate an opposite sex-dependence of thyroxine-binding globulin levels, characterized by increased levels of the protein in the female rats versus increased levels of the protein in the male mice. This is the first report of immunological quantitation of rat and mouse thyroxine-binding globulins.

Characterization of a major development-regulated serum thyroxine-binding globulin in the euthyroid mouse

We confirm our finding of a major development-regulated thyroxine-binding globulin (TBG) in the serum of the euthyroid mouse and investigate a number of its binding, structural and regulatory properties. Between 16 days foetal and 60 days postnatal life, the thyroxine (T4)- and tri-iodothyronine (T3)-binding activities of the sera show a striking ontogenic pattern: the binding is 2-3 times higher in foetuses than in mothers, then further increases after birth, reaching between 3 and 5 days maximum values which are 7-8 times higher than the adult ones. This pattern is not correlated with the ontogenesis of the acknowledged specific (transthyretin, TTR) and non-specific (albumin, alpha 1-foetoprotein) thyroid-hormone carriers of the mouse sera. PAGE studies demonstrate that the protein responsible for the elevated binding of the perinatal period is an alpha 1-globulin, with a migration similar to that of human and rat TBGs. Scatchard analysis is consistent with the notions that the T4-binding sites of TBG have high association constants, about two orders of magnitude above the T4 sites of TTR (10(9) M-1 as against 10(7) M-1) and low capacities (37 and 4 nmol/g of serum proteins in pups and adults respectively). Isoelectric focusing (i.e.f.) demonstrates that mouse TBG is a microheterogeneous protein separable, as a function of the pH gradient, in up to 10-12 isoforms, Marked shifts of the relative abundance of isoforms in the course of development are evidenced. The modulation of the TBG binding activity by non-esterified fatty acids (NEFA) and the control of its synthesis by the thyroid status are also reported. Mono- and poly-unsaturated NEFAs are strong inhibitors of the TBG, although they affect TTR less readily. On the other hand, the biosynthesis and/or secretion of TBG, but not of TTR, is under thyroid-hormone control, experimental hypothyroidism inducing a marked increase of the serum TBG. The TBG of mouse behaves as a highly significant parameter of development, pointing to a likely important function of the protein in the process of maturation. Our finding of major TBGs in both euthyroid rats and mice suggests that TBG is more widely spread than was thought until now, but difficult to detect in certain species outside definite maturation stages.

Gender-related differences of serum thyroxine-binding proteins in the rat

Because little information is available, studies were performed to determine the relationship between gender and sex steroid status on serum T4 binding proteins in the rat. The binding capacity of serum thyroxine-binding globulin was greater in female rats than in male rats (27 +/- 1.3 vs 18.0 +/- 1.3 nmol/l, p less than 0.01) and in fasted female rats than in fasted male rats (64.4 +/- 2.6 vs 30.8 +/- 2.7 nmol/l, p less than 0.01). The binding capacity of serum transthyretin was lower in female rats than in male rats (2.1 +/- 0.1 vs 3.1 +/- 0.1 mumol/l, p less than 0.01). Neither ovariectomy or orchidectomy affected the binding capacity of serum thyroxine-binding globulin and it was not increased in ovariectomized rats treated with estrogen. Orchidectomy did not cause a decrease in the binding capacity of serum transthyretin and testosterone administration did not increase it. In contrast, ovariectomy caused an increase in the binding capacity of serum transthyretin (Intact = 2.2 +/- 0.1 vs ovariectomized = 2.8 +/- 0.1 mumol/l, p less than 0.01) and estrogen administration caused a decrease (ovariectomized = 2.8 +/- 0.1 vs ovariectomized + E2 = 1.9 +/- 0.1 mumol/l, p less than 0.05). The results indicate that the binding capacity of serum thyroxine-binding globulin is higher in female rats than in male rats but this difference is not due to differences in the secretion of gonadal hormones. The binding capacity of transthyretin is lower in female rats than in male rats. This is probably due to the higher circulating levels of estrogen in the female compared to the male.

Differential binding of serum glycoproteins to lectins during hepatic regeneration in hepatocellular carcinoma and fulminant hepatic failure

1. The concentrations of four serum glycoproteins, thyroxine-binding globulin, alpha 2-macroglobulin, alpha 1-antitrypsin and transferrin, as well as their reactivities with concanavalin A and lentil-lectin, were measured in patients with hepatocellular carcinoma or fulminant hepatic failure and in normal subjects. 2. Serum concentrations of thyroxine-binding globulin and alpha 1-antitrypsin were significantly greater in patients with hepatocellular carcinoma than in normal subjects, and the percentage lentil-lectin reactivity of these two proteins was markedly increased. 3. With the exception of transferrin, which did not bind to lentil-lectin, an enhancement of lentil-lectin reactivity was observed for the glycoproteins in serum from patients with fulminant hepatic failure. No difference in concanavalin A binding was found between the groups for any of the glycoproteins. 4. Altered fucosylation, as indicated by increased lentil-lectin binding, occurs in several glycoproteins arising in malignant and non-malignant conditions associated with abnormal hepatic regeneration.

The hepatic biosynthesis of rat thyroxine binding globulin (TBG): Demonstration, ontogenesis, and UP-regulation in experimental hypothyroidism

Using a human thyroxine binding globulin (TBG) cDNA probe, we demonstrate that rat liver contains two TBG mRNA species of different length, consisting of about 1.8 Kb and 2.4 Kb respectively. Slot blot analysis of the hepatic mRNAs from rats of different age reveals a fair correlation between the developmental trend of the messengers and that of the TBG circulating levels. Finally Northern blot and slot blot studies demonstrate that the increase of serum TBG induced in adults by thyroidectomy actually reflects an enhanced hepatic biosynthesis of the protein.

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.

Time-Resolved Immunofluorometric Assay for Thyroxine-Binding Globulin in Serum

We describe a new "sandwich"-type immunofluorometric assay for thyroxine-binding globulin (TBG) in serum. The assay involves a solid-phase monoclonal antibody immobilised in white microtiter wells, and a soluble biotinylated monoclonal antibody that reacts with the captured TBG molecules. Addition of streptavidin labeled with the europium chelator, BCPDA (4,7-bis(chlorosulfophenyl)-1,10 phenanthroline-2,9-dicarboxylic acid), and excess europium results in the formation of a highly fluorescent product. The fluorescence signal of the final complex is quantitated on the dried solid-phase with a pulsed-laser time-resolved fluorometer. The assay requires a 151-fold sample pre-dilution and a total incubation time of 90 minutes. It has a broad dynamic range of 0-100 mg/L and a minimum detection limit of 0.4 mg/L. The coefficients of variation for within-run and between-run assays averaged 4.5% and 5.4%, respectively. The mean analytical recovery of TBG added to serum was 103%. Results obtained by this method correlated well with those determined by a commercial radioimmunoassay (r = 0.96, n = 112) and by an immunoradiometric procedure (r = 0.95, n = 131).

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.

Differential hormone-binding characteristics of thyroxine-binding globulin in hepatocellular carcinoma and cirrhosis

To determine whether previous observations suggesting reduced ability of thyroxine-binding globulin (TBG) to bind exogenous thyroid hormones in hepatocellular carcinoma (HCC) might form the basis of a useful clinical test, we have investigated a larger series involving 49 patients and 10 healthy subjects. The binding ratio (mol hormone bound/mol TBG at a given hormone concentration) for both T 4 and T 3 was significantly reduced when compared to both cirrhotic and normal subjects. No overlap in T 4 binding occurred between HCC patients and the control groups. Serial measurements on serum samples obtained from five cirrhotic patients who ultimately developed HCC revealed significant reductions in binding for both hormones up to 60 months prior to the clinical diagnosis of HCC. A reduced ability to bind thyroid hormones appears to be a specific feature of serum TBG from HCC patients and is one of the earliest alterations seen among cirrhotic subjects who ultimately develop the disease.

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.

Unique Alterations of Thyroid Hormone Indices in the Acquired Immunodeficiency Syndrome (AIDS)

To determine alterations in serum thyroid hormone indices in patients with human immunodeficiency virus (HIV) infection. Prospective, single-blind study. Large metropolitan hospital where 20% of all patients with the acquired immunodeficiency syndrome (AIDS) in Los Angeles are treated. Twenty-six inpatients with bronchoscopy-proven Pneumocystis carinii pneumonia and AIDS. Outpatients included 10 persons seropositive for HIV, 10 with AIDS-related complex, and 10 with AIDS. There were 19 survivors and 7 nonsurvivors of P. carinii infection. Serum triiodothyronine (T3) values generally remained normal until hospitalization, with nonsurvivors having lower values than survivors (0.56 +/- 0.1 nmol/L compared with 1.3 +/- 0.1 nmol/L, P less than 0.002, respectively). Reverse triiodothyronine (rT3) levels were low in persons with AIDS-related complex (0.21 +/- 0.02 nmol/L, P less than 0.001) and in AIDS outpatients (0.17 +/- 0.02 nmol/L, P less than 0.001). Normalization of rT3 occurred after patients were hospitalized (0.28 +/- 0.01 nmol/L). Serum thyroxine-binding globulin values rose with progression of HIV infection (seropositive, 369.7 +/- 18.1 nmol/L, P less than 0.005; AIDS-related complex, 419.1 +/- 37.0 nmol/L, P less than 0.005; AIDS, 423.3 +/- 31.9 nmol/L, P less than 0.005; survivors, 476.3 +/- 24.6 nmol/L, P less than 0.001), whereas nonsurvivors had normal values. All values are compared with normal values (T3, 2.3 +/- 0.04 nmol/L; rT3, 0.28 +/- 0.01 nmol/L; thyroxine-binding globulin, 288.2 +/- 6.9 nmol/L). Infection with HIV produces unique alterations in thyroid function. A progressive decline in rT3 and elevation in thyroxine-binding globulin accompany advancing HIV infection. The persistence of a normal T3 despite progression of HIV infection may contribute to weight loss. A low serum T3 on admission correlates with mortality.

Serum α-fetoprotein and thyroxine-binding globulin in hepatocellular carcinoma

Serum α-fetoprotein and thyroxine-binding globulin in hepatocellular carcinoma

MC-7 A new time-resolved immunofluorometric assay of thyroxine binding globulin in serum: A. Tan, M.J. Khosravi, E.P. Diamandis (CyberFluor Inc., 179 John Street, Toronto, Ontario M5T 1X4)

This paper presents a methodology for semi-automatic extraction of rock discontinuities from point clouds on the resulting 3D digital surface models of rock masses acquired by terrestrial laser scanning or photogrammetry. First, point clouds need to be pre-processed to generate a digital elevation model from a 3D digital surface model of a rock mass. Second, co-directional features of rock discontinuities are identified by classifying the standard deviation of the elevation, slope aspect and slope gradient of raster grids in a digital elevation model using the Iterative Self-organizing Data Analysis Techniques Algorithm (ISODATA). Third, planar features of rock discontinuities are inspected by judging whether the value range of the deviation from the mean elevation (DEV) in the classified subset of raster grids is between + 1 and − 1 using the Topographic Position Index of terrain analysis. Fourth, point clouds data corresponding to the target surfaces of rock discontinuities are acquired by data post-processing using the ArcToolbox of ArcGIS. Finally, geological analysis is executed by calculating the geometric features of the extracted point clouds. A case study of a rock slope along a highway is presented using the proposed method, the results of which demonstrate that the proposed method is so rapid and accurate that it could greatly reduce the amount of manual labour, improve the efficiency of surveying, and utilize the powerful terrain analysis and visualization capabilities of ArcGIS to avoid the computational challenges associated with directly analysing point cloud data.

Sex hormone-binding globulin and thyroxine-binding globulin levels in premature thelarche

Premature thelarche is defined as the isolated development of breast tissue in girls less than 8 years of age. Although breast development is an estrogen-dependent process, these girls do not have elevated serum estrogen levels, and the hormonal basis for their condition is unclear. We studied the levels of two estrogen-dependent transport proteins, sex hormone-binding globulin (SHBG) and thyroxine-binding globulin (TBG), in order to determine if there was evidence for a more subtle estrogen effect in girls with premature thelarche. SHBG levels in girls with premature thelarche were not significantly different from those of prepubertal girls of the same ages and were significantly lower than those in girls undergoing pubertal development at the appropriate age (P < 0.05) and in normal women (P < 0.001). There was no statistically significant difference in TBG levels between the girls with premature thelarche and prepubertal controls. There was also no significant difference in TBG levels between prepubertal girls and girls in early puberty. In contrast, women had TBG levels that were significantly lower than those in all girls studied. We conclude that the estrogen exposure (whether endogenous or exogenous) of girls with premature thelarche is less than that of girls in early true puberty and similar to that of other prepubertal girls. Further, changes in serum TBG are not as sensitive an indicator of estrogen effect as is breast development or changes in SHBG. This study also suggests that large amounts of exogenous estrogens are not an element in the development of premature thelarche.