INHERITED DECREASE OF THE BINDING CAPACITY OF THYROXINE-BINDING GLOBULIN (TBG)

1970 ◽  
Vol 64 (1) ◽  
pp. 171-180 ◽  
Author(s):  
O. P. Heinonen ◽  
B.-A. Lamberg ◽  
J. Virtamo

ABSTRACT A family with a decrease in the binding capacity of thyroxine binding globulin (TBG) is described. The gene was probably transmitted by a female who married twice. Five subjects were considered TBG deficient, with TBG values ranging from 8.4 to 16.8 μg/100 ml. Of these subjects 2 were males and 3 females; the males had the lowest binding capacities. In addition, 1 male and 3 females had TBG values within the low normal range and were considered as possibly affected. The mode of inheritance could not be exactly defined but there were indications that it might be an autosomal dominant. The correlation of TBG to the protein-bound iodine in the serum (PBI), to the triiodothyronine uptake by Sephadex (T3-U), to the ratio between them (T3-U/PBI), and to the proportionate free thyroxine (PFT4) was strongly positive or negative. A gradual change in these variables from the affected to the unaffected subjects was observed. These correlations indicated that in normal subjects TBG is the most important factor governing the PBI and free thyroxine levels. In addition, a strong inverse and statistically significant correlation was observed between the binding capacity of TBG and that of the pre-albumin (TPBA). The difference between affected and unaffected subjects with regard to TPBA was also statistically significant.

1979 ◽  
Vol 91 (1) ◽  
pp. 70-76 ◽  
Author(s):  
Paul Bratusch-Marrain ◽  
Hannes Haydl ◽  
Werner Waldhäusl ◽  
Robert Dudczak ◽  
Wolfgang Graninger

ABSTRACT A kindred is presented in which 4 members in 3 generations showed absent or reduced serum concentrations of thyroxine-binding globulin (TBG). TBG was undetectable by radioimmunoassay in one male and decreased to varying extent in 3 female patients (4.0, 4.2 and 8.6 μg/ml; normal range 12.5–26.0 μg/ml). Total thyroxine serum concentrations in the affected subjects were well in the hypothyroid range without clinical evidence of hypothyroidism. The mode of transmission of the trait was consistent with X-chromosome linkage. A high incidence of non-toxic goitre was also present in most of the family members examined irrespective of TBG levels. The transmission of the goitre trait was compatible with autosomal dominant inheritance. Thus its association with transmission of TBG deficiency was interpreted as not causal but coincidental.


1977 ◽  
Vol 84 (4) ◽  
pp. 750-758 ◽  
Author(s):  
J. F. Finucane ◽  
R. S. Griffiths ◽  
E. G. Black ◽  
C. L. Hall

ABSTRACT Serum concentrations of total and free thyroxine and triiodothyronine together with urine losses of unconjugated thyroid hormones have been measured in normal subjects and in patients with renal disease. Serum total hormone values in the hypothyroid range were common in the renal group and correlated inversely with the degree of renal impairment but not with renal loss of hormone which in the case of thyroxine exceeded the average normal daily loss ten-fold. The euthyroid state of patients with renal disease was best reflected by serum free thyroxine concentration which in every case was within the normal range. Poor correlation was apparent between the respective urine concentrations of albumin and thyroxine, and the reasons for this are discussed.


1986 ◽  
Vol 112 (2) ◽  
pp. 192-196 ◽  
Author(s):  
D. B. Ramsden ◽  
D. N. Crossley

Abstract. Some factors influencing serum 3,5,3',5'-tetradiodothyroacetate (T4A) concentrations were examined in hypothyroid, euthyroid and hyperthyroid human subjects. Serum T4A concentration was shown to be correlated with parameters such as serum, total and free thyroxine (T4) concentrations and thyroxine: thyroxine binding globulin ratio, which are indicative of the availability of T4 for peripheral metabolism. The relationship between T4A and these parameters was not a simple linear one; serum levels of T4A tended to show less variation from the normal range than did serum total T4 in hyperthyroid subjects.


1971 ◽  
Vol 17 (3) ◽  
pp. 174-182 ◽  
Author(s):  
Norman D Lee ◽  
Boris Catz ◽  
M S Margolese ◽  
Vincent J Pileggi

Abstract Various indexes of thyroid status were measured in sera from normal men and women, normal women who were using oral contraceptives, hyper- and hypothyroid patients, and hypothyroid patients being successfully managed with various forms of replacement therapy. Total circulating thyroxine concentrations were measured by three methods as well as the thyroxine-binding capacity of the serum inter-alpha globulin, "free" thyroxine, and "free" thyroxine index. Our purpose was to compare the various measurements, and to assess their diagnostic usefulness. The most significant finding was that, of 197 hypothyroid patients, all of whom possessed total circulating thyroxine concentrations within normal limits, 28% showed subnormal "free" thyroxine concentrations.


1975 ◽  
Vol 21 (10) ◽  
pp. 1388-1392 ◽  
Author(s):  
Melvin R Stjernholm ◽  
Robert N Alsever ◽  
Merritt C Rudolph

Abstract We compared the free-thyroxine index in normal adults and in euthyroid patients taking diphenylhydantoin. All subjects had normal serum thyrotropin concentrations. Serum thyroxine concentrations were determined by two commonly used competitive protein-binding assays, which yielded slightly different values, but which consistently showed the same degree of decrease in mean serum thyroxine concentration in drug-treated patients as compared to the normal subjects. When 14C-labeled diphenylhydantoin was added to serum before the assay, it was separated from thyroxine in the Ames method, whereas by the Murphy-Pattee method both drug and thyroxine were extracted together. Thus, the decrease in serum thyroxine concentrations during diphenylhydantoin therapy cannot be the result of drug interference with the binding of thyroxine to binding proteins in the assays. Triiodothyronine uptake, evaluated by two methods, was identical in the two groups. The free-thyroxine indexes for all normal persons were within the manufacturer's normal range, but 21% of the drug-treated patients had subnormal indexes by the Ames method; the indexes as measured by the Murphy— Pattee method were in the lower half of the normal range. Because the triiodothyronine uptake was unaffected by the drug treatment, the decreases in the indexes must have resulted from the lower serum thyroxine concentrations. We conclude that the free-thyroxine index may not provide a valid estimate of either the clinical status or the free-thyroxine concentration in patients taking diphenylhydantoin.


1982 ◽  
Vol 201 (2) ◽  
pp. 259-266 ◽  
Author(s):  
John S. Hill ◽  
William H. Sawyer ◽  
Geoffrey J. Howlett ◽  
James S. Wiley

Human erythrocytes possess a lattice work of extrinsic proteins on the inner face of the membrane (‘cytoskeleton’) that maintains the shape and deformability of the cell. The major proteins of the cytoskeleton are spectrin and actin, which are attached to the membrane by protein bands 2.1 (‘ankyrin’) and 4.1. The interactions of spectrin/actin with erythrocyte membranes from normal subjects and from patients with hereditary spherocytosis (HS) have been studied by using an air-driven ultracentrifuge, which can rapidly separate membranes from soluble proteins (150000g for 30s). The total amount of spectrin/actin in HS and normal ghosts is similar. However, the rate of dissociation of spectrin and actin from HS erythrocyte membranes at low ionic strength is significantly lower than that observed for normal membranes. Spectrin and actin isolated from either HS or normal membranes re-associated in a similar manner to spectrin/actin-depleted vesicles prepared from normal cells. Scatchard analysis showed an average binding capacity of 278μg/mg of membrane protein. However, spectrin/actin-depleted vesicles prepared from HS cells bound significantly less spectrin/actin prepared from either the normal or abnormal cells (average binding capacity 158μg/mg of membrane protein). The defect was defined further by studying the cytoskeleton obtained by Triton X-100 extraction of membranes. Under conditions of low ionic strength cytoskeletons prepared from HS membranes dissociated more slowly than those prepared from normal membranes, and only 80% of the protein from HS cytoskeletons could be solubilized after 180min compared with 100% for normal cytoskeletons. The difference between HS and normal membranes, which persists in isolated cytoskeletons, suggests that alterations in either the primary structure or the degree of phosphorylation of protein bands 2.1 or 4.1 may be central to the molecular basis of hereditary spherocytosis.


1969 ◽  
Vol 15 (5) ◽  
pp. 367-375 ◽  
Author(s):  
R C Roberts ◽  
T F Nikolai

Abstract Thyroxine-binding globulin (TBG) assays by the polyacrylamide electrophoresis assay of Nikolai and Seal have been carried out on 315 normal subjects. The assay was carried out with 200 µg exogenous labeled thyroxine per 100 ml added to the samples. The means and standard deviations for the three thyroxine-binding proteins in males (n = 140) were: TBG 19.7 ± 3.0 µg/100 ml, thyroxine-binding albumin (TBA) 38.0 ± 10.3 µg/100 ml, thyroxine-binding prealbumin (TBPA) 141.2 ± 10.9 µg/ 100 ml. The values for females (n = 175) were: TBG 21.6 ± 3.2 µg/100 ml, TBA 40.0 ± 10 µg/100 ml, and TBPA 137 ± 10.5 µg/100 ml. The difference in the means of the TBG values of males and females was significant (p < 0.01). Partial correlation analysis indicated that a significant correlation existed between protein-bound iodine and the TBG values only. A highly significant correlation was also found between the resin T3 uptake values and TBG. Persons (n = 43) receiving estrogens had a mean TBC of 36 µg/100 ml with a range of 26-45. This is an elevation of almost 5 SDs above normal. The normal values obtained by the polyacrylamide assay are compared with other electrophoretic assays of TBG.


1990 ◽  
Vol 29 (01) ◽  
pp. 40-43 ◽  
Author(s):  
W. Langsteger ◽  
P. Költringer ◽  
P. Wakonig ◽  
B. Eber ◽  
M. Mokry ◽  
...  

This case report describes a 38-year-old male who was hospitalized for further clarification of clinically mild hyperthyroidism. His increased total hormone levels, the elevated free thyroid hormones and the elevated basal TSH with blunted response to TRH strongly suggested a pituitary adenoma with inappropriate TSH incretion. Transmission computed tomography showed an intrasellar expansion, 16 mm in diameter. The neoplastic TSH production was confirmed by an elevated alpha-subunit and a raised molar alpha-sub/ATSH ratio. However, T4 distribution on prealbumin (PA, TTR), albumin (A) and thyroxine binding globulin (TBG) showed a clearly increased binding to PA (39%), indicating additional prealbumin-associated hyperthyroxinemia. The absolute values of PA, A and TBG were within the normal range. After removal of the TSH-producing adenoma, basal TSH, the free thyroid hormones and T4 binding to prealbumin returned to normal. Therefore, the prealbumin-associated hyperthyroxinemia had to be interpreted as a transitory phenomenon related to secondary hyperthyroidism (T4 shift from thyroxine binding globulin to prealbumin) rather than a genetically conditioned anomaly of protein binding.


1969 ◽  
Vol 21 (01) ◽  
pp. 134-143 ◽  
Author(s):  
W. D Walls ◽  
M. S Losowsky

SummaryA kinetic method for the quantitative estimation of plasma F.S.F. activity is described and discussed.This method was applied to normal subjects and to patients with chronic liver disease. The plasma F.S.F. activity was uninfluenced by either sex or age, and the normal range has been defined.A significant decrease in plasma F.S.F. activity was observed in patients with chronic liver disease. Subnormal levels of activity were found in 25% of such patients but were unrelated to episodes of abnormal haemorrhage. Plasma F.S.F. activity tended to be lower in patients with disease of greater clinical severity. In 2 patients showing clinical improvement there was an increase in plasma F. S. F. activity.It was confirmed that plasma fibrinogen levels increase with age.


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