Thyroxine-binding Globulin Capacity Research Articles

Circulating thyroid hormones in progressive renal failure in the baboon (Papio ursinus).

In order to examine the effects of developing renal failure on circulating thyroid hormones, serum concentrations of thyroxine (T4), free T4 (FT4), triiodothyronine (T3) and reverse T3 (rT3) and TBG capacity were measured in 9 baboons before and during the progress of acute (mean survival 12 days), subacute (32 days) and chronic (120 days) renal failure following allogeneic renal transplantation. Irrespective of the rate of development of renal failure, there were significant, non linear (power functions) negative correlations between serum creatinine or urea concentrations and levels of T4, FT4 and T3; rT3 levels remained unchanged, but the T4: rT3 molar ratio fell from 236.5 +/- 61 (+/- SE) to 121.8 +/- 30.9 (p less than 0.05). T4 and T3 levels were invariably subnormal at creatinine concentrations greater than 250 mumol/l (2.8 mg/dl), but FT4 was subnormal only in chronic renal failure. Thyroxine binding globulin (TBG) capacity did not change significantly; thus the TBG: T4 ratio increased from 3.4 +/- 0.2 (basal) to 10.4 +/- 3.4 before death (p less than 0.05). In animals which survived for greater than 25 days after transplantation, a significant linear correlation between FT4 and T3 was found as uremia progressed. Polyacrylamide gel electrophoresis (pH 7.4) of (125I)-T4 labelled preoperative and uremic serum showed a consistent decline in the proportion of tracer bound to TBG, from 67.0 +/- 0.8% to 58.9 +/- 1.0% (p less than 0.001), with a 48% reduction in TBG saturation (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Action of human growth hormone (hGH) on extrathyroidal conversion of thyroxine (T4) to triiodothyronine (T3) in children with hypopituitarism.

To study the action of human growth hormone (hGH) on peripheral metabolism of serum thyroxine (T4), an oral loading dose of levothyroxine (1.2 mg/m2) was administered to seven children with hypopituitarism before initiation of hGH therapy. Serum concentrations of triiodothyronine (T3), T4, reverse triiodothyronine (rT3), and thyroxine-binding globulin (TBG) capacity were measured sequentially for 6 days. The study was repeated after 4 wk of treatment with hGH. Serum concentrations of T4 were not affected by hGH therapy. In contrast, mean basal serum concentration of T3 increased significantly after treatment with hGH. Also, changes in serum concentrations of T3 and in the ratio of T3/T4 after an oral dose of levothyroxine were significantly augmented during hGH therapy. Serum concentrations of rT3 changed in the opposite direction of T3 during therapy. After treatment with hGH, the mean basal level of serum rT3 decreased, and increases in serum concentrations of rT3 after oral levothyroxine were significantly attenuated. No changes in mean serum concentrations of thyroid stimulating hormone (TSH) and TBG capacity were observed. These data suggest that administration of hGH to children with hypopituitarism enhances the extrathyroidal conversion of T4 to T3 and concomitantly decreases the serum concentration of rT3.

Thyroxine-binding globulin capacity and concentration evaluated from blood spots on filter-paper in a screening program for neonatal hypothyroidism.

We describe a simple method for evaluating thyroxine-binding globulin capacity and concentration from a single 1-cm blood spot on filter-paper used in a screening program for neonatal hypothyroidism. This method permits prompt diagnosis of about 90% of the infants with thyroxine-binding globulin deficiency in our abnormal low-thyroxine, low-thyrotropin population. There was excellent equivalence between results obtained by our method and by the method of Chopra et al. (J. Clin. Endocrinol. Metab. 35:565, 1972), and minimal overlap between the population with low thyroxine-binding globulin and the low-thyroxine, normal thyrotropin population. We recommend this method to all programs in which a primary thyroxine measurement is used in screening for congenital hypothyroidism.

Thyroxine-binding globulin capacity and concentration evaluated from blood spots on filter-paper in a screening program for neonatal hypothyroidism.

Abstract We describe a simple method for evaluating thyroxine-binding globulin capacity and concentration from a single 1-cm blood spot on filter-paper used in a screening program for neonatal hypothyroidism. This method permits prompt diagnosis of about 90% of the infants with thyroxine-binding globulin deficiency in our abnormal low-thyroxine, low-thyrotropin population. There was excellent equivalence between results obtained by our method and by the method of Chopra et al. (J. Clin. Endocrinol. Metab. 35:565, 1972), and minimal overlap between the population with low thyroxine-binding globulin and the low-thyroxine, normal thyrotropin population. We recommend this method to all programs in which a primary thyroxine measurement is used in screening for congenital hypothyroidism.

4 Investigation and treatment of hypothyroidism

INVESTIGATION The investigation of patients with suspected hypothyroidism falls naturally into two stages. Preliminary investigation is required to determine the level of thyroid function and confirm, or refute, a clinical diagnosis of thyroid failure, and the use of other diagnostic procedures is required to identify the cause of hypothyroidism in some patients. Tests to Determine the Level of Thyroid Function The laboratory techniques available for assessing the level of thyroid function fall into three groups and the use of each allows different aspects of impaired thyroid function to be defined. The three groups of techniques are: tests of thyroid function; tests of peripheral tissue function; and tests of hypothalamic--pituitary function. The techniques have been reviewed in detail elsewhere (Evered, 1974, 1976). Tests of thyroid function Direct or indirect techniques for measuring circulating thyroid hormone concentrations have been widely available for many years. Serum thyroxine (T4) concentration may be measured by a competitive protein binding assay (Murphy, 1965) or by radioimmunoassay (Mitsuma et al, 1972). These procedures measure total serum T4 concentration, and thus alterations in thyroxine-binding globulin (TBG) capacity (e.g. pregnancy, oral contraceptive therapy, liver disease, etc.) may lead to total hormone concentrations which are at variance with the clinical assessment of the patient. The serum T4 concentration can, however, be corrected for changes in TBG by carrying out a thyroid hormone binding test (e.g. T3 resin uptake, T3 Sephadex uptake), which will estimate residual TBG capacity and may be used to calculate a free thyroxine index (FTI) (Clark and Horn, 1965). The older technique of estimating the protein-bound iodine (PBI) concentration also

Sex steroids and thyroid function tests: the role of estrogen and progestogen.

Thyroid functions were evaluated in 102 14-47 year old women (mean age 28.3 years by comparing changes during administration of estrogen (.08 mg ethinyl estradiol; 1.25 mg Premarin) progestogen (4 mg chlormadinone acetate; 10 mg dydrogesterone) and a combination of estrogen and progestogen (1 mg norethindrone .05 mg mestranol; .5 mg ethynodiol diacetate 1 mg mestranol). Total thyroxine (T4) concentrations were significantly elevated in women receiving estrogen and estrogen-progestogen. Parallel increases of total triiodothyronine (T3) were observed in women in the estrogen groups except for those receiving conjugated estrogen. The use of estrogens resulted in decreased T3 resin uptake values and increased thyroxine-binding globulin (TBG) capacity levels thus showing the negative correlation between these determinations. In the ethinyl estradiol and mestranol-norethindrone groups the free thyroxine index (FTI) calculated by dividing the total T4 by the total TBG fell within normal ranges. No significant changes of total T4 total T3 T3 resin uptake TBG capacity and FTI values were noted in women taking progestogen. Serum levels of thyroid-stimulating hormone were normal in women taking estrogen and/or progestogen.(AUTHORS MODIFIED)

Alterations in Serum Thyroid Hormones and Thyroxine-Binding Globulin in Patients with Nephrosis*

Serum concentration, T4-binding capacity, and affinity of thyroxine-binding globulin (TBG) were studied in 10 adult males with the nephrotic syndrome who were not receiving corticosteroid therapy. There was a significant correlation (r =-0.81,P<0.001) between the degree of proteinuria and the daily urinary excretion of TBG. The only subject who showed low serum TBG concentration and capacity had the severest degree of proteinuria (24 g⁄day). In all of the other patients the serum concentration and T4-binding capacity of TBG were within the normal range despite significant urinary losses of TBG. There was a tendency to lower TBG affinity values for T4 as compared to the control group, but the mean did not reach statistical significance. The nephrotic group as a whole exhibited an abnormally high fraction of dialyzable T4 and free T4 concentration in serum, but the mean total serum T4 was normal. The mean urinary excretion of T4 was 69 μ⁄day. Only two cases had low total serum T4, one of these having a low ...

Thyroid Function and Metabolic State in Chronic Renal Failure

Thirty-eight patients with chronic renal insufficiency who were in a dialysis program underwent studies of thyroid function and metabolic status. Mean values for serum total and free thyroxine (T4) concentrations and thyroxine-binding globulin capacity were within normal limits. Although mean serum total triiodothyronine (T3) concentration was normal, 43% of the group had low serum T3 and 54% had low serum free T3 concentrations. Serum thyrotrophin (TSH) concentrations were normal in all but four subjects who had very slight elevations. Metabolic status was assessed by various metabolic tests; mean values for each of these tests were normal, and the clinical index scores indicated that all patients were euthyroid. Results of metabolic testing were similar in patients with low and those with normal serum T3 concentrations. Low serum T3 measurements did not accurately reflect metabolic state in patients with chronic renal failure, whereas serum free T4 and TSH concentrations were reliable indicators of thyroid state.

Clinical evaluation of new indicators of free thyroxine concentration and thyroxine-binding globulin capacity

A rapid and simple method is described for the indirect measurement of free thyroxine (T 4) concentration and maximal thyroxine-binding globulin (TBG) capacity applying a single kit of Thyopac-4. Initially, a value for total T 4 is determined, after which the patient's serum is added to permit estimation of T 4 corrected for abnormal TBG concentration. The ratio of increased radioactiyity in the supernatant after the addition of patient's serum to that obtained using pooled normal serum is designated the TBG index, being directly related to the amount of TBG in the added serum. The index is significantly increased in hypothyroidism and pregnancy, and decreased in hyperthyroidism, correlating well with the TBG capacity measured by reverse-flow paper electrophoresis. A free T 4 index (FTI) can be calculated from the values for T 4 and TBG index, because the TBG index is reciprocally related to the serum uptake test (T 3 -resin). Values for FTI are significantly increased and decreased in hyperand hypothyroidism, respectively, whereas they remain within the normal range in pregnancy and TBG deficiency. The FTI is shown to bear a nearly straight-line relationship to that calculated from separate estimations of T 4 and the serum uptake test (T 3-resin).

Evaluation of new kits for the assessment in vitro of thyroid function by determination of serum total thyroxine, free TBG capacity, and free thyroxine index Sephadex G-25 and 125I-labelled triiodothyronine and thyroxine.

A trial was carried out on 134 patients of new kits (Ames Co) using columns of Sephadex G-25 for the determination of serum total thyroxine (Tetralute test) and for the indirect estimation of serum free thyroxine-binding globulin capacity (Trilute test). Both new methods were quicker and easier than the reference resin methods and of similar precision. The two measurements when combined to give a free thyroxine index (Trilute-Tetralute-FTI) increased further the diagnostic discrimination and usefulness of the tests. The method for the determination of serum thyroxine can be modified to give a direct estimate of serum free thyroxine, expressed as a free thyroxine index. This new single-column technique, called the ;single-column free thyroxine index', gave a good correlation with clinical thyroid status in a preliminary trial of 45 patients.

A New Index of Thyroxine Binding Globulin (TBG) by Thyopac-4 kit, and its Evaluation by Maximal TBG Capacity Measured by Reverse Flow Paper Electrophoresis

Thyopac-4キットによる簡易なTBG Indexの新算出法を考案し, 各種の甲状腺機能状態の患者血清について本IndexおよびT3レジン摂取率並びに逆流炉紙電気泳動法によるTBGの最大結合能を測定して, これらの相互関係を追究した.本IndexはT3レジン摂取率及びTBGの最大結合能の両者に有意の相関を有したが, その変動はむしろ後者に類似し, その関係は必ずしも直線的ではないが, TBG変動のIndicatorとなることが示された.本Indexは, 同時に同一キットによつてT4値及びFree T4 Indexが測定され, 日常の簡易検査法として有用と考えられた.

Study of Four New Kindreds with Inherited Thyroxine-Binding Globulin Abnormalities POSSIBLE MUTATIONS OF A SINGLE GENE LOCUS

Five families with inherited thyroxine-binding globulin (TBG) abnormalities were studied. On the basis of serum thyroxine (T(4))- binding capacity of TBG in affected males, three family types were identified: TBG deficiency, low TBG, and high TBG capacity. In all families evidence for X-linked inheritance was obtained and in one family all criteria establishing this mode of inheritance were met. Only females were heterozygous, exhibiting values intermediate between affected males and normals. Overlap in heterozygotes was most commonly encountered in families with low TBG. QUANTITATIVE VARIATION IN THE SERUM CONCENTRATION OF FUNCTIONALLY NORMAL TBG WAS DEMONSTRATED BY: (a) failure of serum from TBG-deficient subjects to react with anti-TBG antibodies; (b) normal kinetics of T(4) and triiodothyronine-binding to TBG in sera from subjects with low TBG and high TBG capacity; (c) concordance of estimates of TBG concentration by T(4) saturation and by immunological methods; and (d) normal rate of heat inactivation of TBG. No abnormalities in serum transport of cortisol, testosterone, aldosterone, or thyroxine bound to prealbumin could be detected. These observations suggest that all the TBG abnormalities thus far observed reflect mutations at a single X-linked locus involved in the control of TBG synthesis.

CLINICAL AND LABORATORY OBSERVATIONS IN CASES OF TRIIODOTHYRONINE TOXICOSIS CONFIRMED BY RADIOIMMUNOASSAY

Forty patients with triiodothyronine (T3) toxicosis have been identified. All were clinically hyperthyroid with raised levels of both total and free T3 but normal serum concentrations of total and free thyroxine and normal thyroxine-binding globulin capacities. Twenty-nine presented as Graves' disease, eight as autonomous adenoma, and three as toxic multinodular goitre. The availability of the radioimmunoassay for T3 should permit more frequent recognition of this disorder.

Separation of thyroxine-binding proteins in human serum at pH 7.4. II. Effect of pH and temperature on the bindng capacities of thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA).

ABSTRACT The binding capacities of human serum TBG and TBPA have been shown in this study to be pH-dependent. In polyacrylamide gel electrophoresis at 5 C the mean TBG maximum binding capacity (MBC) for 6 individual sera was 18.5± 3.5(S.D.) μg/100 ml at pH 7.4 and 12.3 ± 1.9 μg/100 ml at pH 9.0. The increased binding capacity at physiologic pH parallels previously demonstrated tracer T4 binding by TBG at pH 7.4. The MBC of TBPA was 207 ± 31 μg/100 ml at pH 7.4 and 308 ± 32 μg/100 ml at pH 9.0, in accord with earlier tracer T4 studies which showed enhanced TBPA binding at alkaline pH. Albumin binding in the present experiments was unaffected by pH. The fact that TBG and TBPA MBCs are pH-dependent suggests that the number of available binding sites for T4 on these proteins changes with pH. Studies of the effect of temperature on TBG and TBPA binding capacities showed TBG MBC at pH 7.4 to be about 20% lower at 37 C compared with 5 C. However, at pH 9.0 the binding capacity for TBG at 37 C was 35% to 70% belo...

Effects of oestrogens on serum thyroxine-binding globulin capacity and on the peripheral metabolism of thyroxine in patients with hepatic cirrhosis.

ABSTRACT The effects of oestrogens on serum thyroxine-binding globulin (TBG) capacity and on the peripheral metabolism of thyroxine were studied in patients with hepatic cirrhosis as well as in a group of normal subjects. Oestrogens increased TBG capacity in cirrhosis from 24.7 to 38.4 μg/100 ml whereas in normal subjects TBG capacity was raised from 22.8 to 48.6 μg. While the fractional turnover of thyroxine in cirrhosis did not change with the administration of oestrogens, the space of distribution was reduced. As a result of these changes, the extra-thyroidal thyroxine pool was similar to the pre-treatment values and hence the daily degradation rate of thyroxine remained unchanged.

Changes in triiodothyronine kinetics produced by variations of serum thyroxine-binding globulin capacity in subjects without thyroxine.

ABSTRACT The kinetics of 125I-T3 during a 72-hr period were studied in 8 athyreotic subjects maintained on an average dose of 75 μg of T3 daily, thereby eliminating T4 competition. In a control study, T3 half-time was 29.8 hr, fractional turnover rate 2.4%/hr, space of distribution 36.0 liters and clearance rate 0.85 liters%hr. The administration of estrogens produced no significant variations of these parameters. On the other hand, diphenylhydantoin induced a decrease in T3 half-time (p <0.05) and an increase in the space of distribution (p <0.01) and clearance (p <0.01). Of these patients 4 were restudied after taking physiological doses of T4 and T3. There was a slight but significant increase in T3 half-time (p <0.01), and nonsignificant enlargement of the space of distribution and decrease in clearance as compared to the pre-T4 control studies. Similar and more pronounced changes were observed when diphenylhydantoin was given with T4. It is concluded that, even though T3 binding by TBG in vivo does o...

Dolphin thyroid: Some anatomical and physiological findings

1. Plasma thyroxine (T4), protein bound iodine (PBI), inorganic iodine, total iodine, thyroxine binding globulin (TGB), unsaturated TBG (resin T3 uptake test) and free thyroxine were measured in a series of tests on two species of porpoise (or dolphins) and two species of small whales. This was the first such work done on cetaceans. The values presented for the bottlenose dolphin, Tursiops truncatus, were derived from 86 plasma specimens from 31 different animals (Table 2) and should be clinically useful for the future diagnosis of thyroid disease in that species. 2. A total of twenty-four plasma specimens from the Pacific white-striped dolphin, Lagenorhynchus obliquidens (Fig. 3), the killer whale Orcinus area (Fig. 4) and the pilot whale Globicephala scammoni (Fig. 5) gave values that must be regarded as preliminary until a larger number of animals can be sampled. 3. All of these marine cetaceans have larger thyroids and smaller body surface areas than terresterial mammals of comparable weight. 4. In bottlenose dolphins and Pacific white-striped dolphins the total thyroid weight is about 2.25 times the total adrenal gland weight. The adrenals and the thyroid are both about one-third larger (on a gland weight to body weight basis) in Pacific white-striped dolphins. 5. Differences in water temperature of 6° C to 9° C did not appear to affect the plasma thyroid indices of bottlenose dolphins or killer whales (Fig. 4). A 72-hour fast caused an increase in plasma T4 levels of each of 3 bottlenose dolphins with an average rise of 1.2 μg/100 ml. 6. The high level of plasma T4 and PBI appear to correlate well with the relatively high metabolic rate observed in T. truncatus. However, the species that appears to have the highest metabolic rate, the Pacifie white-striped dolphin, Lagenorhynchus obliquidens (Fig. 3), had the lowest plasma level of T4, PBI, total iodine, TGB capacity and cholesterol (Table 2). This data points out the need for a comprehensive study of thyroid function in wild and captive white-striped dolphins and other species that are difficult to maintain in captivity.

Metabolic effects of mestranol in high dosage

Metabolic effects of mestranol, given in continuous high dosage for 3 or more months, were investigated in 4 postmenopausal women with metastatic breast cancer. Three women improved subjectively; in 1 patient objective remission of disease occurred. Adverse effects included: peripheral edema, weight gain of variable duration, hypertension, pruritus, increased skin pigmentation. In 1 patient, at 1 and 2 months of treatment, bromsulphthalein retention occurred; serum bilirubin, glutamic-oxalacetic transaminase and alkaline phosphatase levels were increased transiently. These values returned to normal by 4 months, and remained normal for almost 3 years of treatment. With treatment, average values of plasma cholesterol were increased slightly, phospholipid levels were 20% greater, and triglycerides increased 40%. Circulating free fatty acid levels were decreased. Plasma alpha-lipoprotein increased by 40%. Blood sugar values were less. Plasma cortisol increased greatly; plasma growth hormone increased 3-fold: urinary gonadotrophin excretion diminished. There was a modest increase in serum protein-bound iodine values; thyroxine-binding globulin capacity doubled.

Increased serum thyroxine-binding globulin capacity: inheritance and linkage relationships.

ABSTRACT The binding capacity of thyroxine-binding globulin (TBG) has been measured in 60 members of a kindred. The data strongly suggest X-linked inheritance of the trait for elevated TBG binding capacity. The results of blood grouping tests indicate that the X-linked Xg locus is not closely linked to the locus for increased TBG capacity.

Effects of variations of thyroxine-binding globulin capacity on the disappearance of triiodothyronine from the plasma.

In a previous study from our laboratories alterations in TBG binding capacity were found not to alter the rate of egress of T3 from the circulation for the first hour after intravenous injection. It was considered of interest to study the fate of triiodothyronine after it reached equilibrium in its ultimate distribution space. The T3 half-time was obtained by extrapolating the rectilinear portion of the curve for blood radioactivity from the end of the second to seventh day after injection of a tracer dose. Data were obtained from 20 normal subjects, 15 estrogen-treated patients, 12 patients who were treated with androgens (5 of whom also received an anabolic agent), 7 patients treated with diphenylhydantoin. The doses used were sufficient to alter significantly the TBG binding capacity of the serum. In the estrogen-treated group the TBG capacity was increased; in the other 2 treated groups it was decreased. The mean T3 half-time determined from blood radioactivity was as follows: normal—1.60 days; estrogen-treated group—1.35 days; androgenanabolic agent group—2.09 days; diphenylhydantoin-treated group—2.11 days. These results are opposite to those that would be expected if plasma binding were the most important factor contributing to the fate of T3. Thus, other factors, e.g., tissue binding or cellular handling, must have a major influence on T3 turnover.