TBG Levels Research Articles

A TBG-deficient family with a male exhibiting decreased but not zero TBG levels.

A TBG-deficient family with a male exhibiting decreased but not zero TBG levels.

PARTIAL THYROXINE-BINDING GLOBULIN DEFICIENCY IN A FAMILY

Deficiency of thyroxine-binding globulin (TBC) has been previously described in several families, and the mode of inheritance in most families has been interpreted as X-linked. The hemizvgous affected males have an absence of TBC, while the heterozygous females have wide range of TBC values (low to normal). A family recently studied by us presents a different form of TBG deficiency. The proband, who was born with ambiguous external genitalia and raised as a female, was found to have a testis on one side and a streak gonad on the other side. Her chromosome constitution showed a mosaicism of XYY/XY/XO. After a low PBI level was obtained, she was found to have reduced but not absent TBG activity. Similar reduction of TBC was found in her brother, who also had congenital hypothyroidism, and her normal male first cousin. The observation of the reduction of TBG levels rather than a total absence in the hemizygous affected individuals in this family suggests a variant of TBG deficiency, although it still appears to be due to an X-linked gene and is most likely due to an allele of the same gene.

THYROXINE SECRETION RATE DURING INFANCY: EFFECT OF ESTROGEN.

Measurements of thyroxine secretion rate have been conducted by the thyroid I131 blockage method in 17 premature infants. The infants were 24–65 days of age at the beginning of the study; normal thyroid function was indicated by normal initial radioiodine uptake studies. Mean daily thyroxine secretion rate in 13 infants determined by calculation of the regression line of daily thyroidal radioiodine release on increasing doses of thyroxine was 18.6 μg thyroxine/kg/day. The regression lines were not significantly different with and without perchlorate administration, indicating that recycling of radioiodine does not produce significant error. The thyroxine secretion rate of 18.6 μg/kg/day is considerably higher than adult human values by the serum specific activity method. In 5 infants given estradiol benzoate with a concomitant thyroid blocking dose of sodium l-thyroxine, stimulation of radioiodine released occurred. This stimulation was associated with increasing BEI values, suggesting an increase in TBG levels. Mean triiodothyronine I131 resin uptake values, however, increased during the therapy period, indicating endogenous thyroid hormone secretion predominating over the increase in TBG and progressively saturating available protein binding sites. The increased thyroidal radioiodine release rate, which occurred in spite of increasing triiodothyronine I131 resin uptake values, suggests a direct stimulation of hypothalamic-pituitary TSH release by estradiol benzoate.

Familial elevation of serum thyroxine-binding capacity.

A family is described in which members in 3 generations showed serum protein-bound iodine levels well above the normal range without evidence of hypermetabolism. The saturation capacity of the serum thyroxine-binding globulin fraction (TBG) was grossly elevated in the affected cases ro valres usually observed only in pregnancy and after estrogen therapy. The 3 children investigated, one of whom shewed elevation of the TBG, had saturation values of the pre-albumin thyroxine-binding proteins (TBPA) well below the normal range accepted for normal adults, and this also wao found in a small series of children without thyroid abnormality. The incidence of the elevated-TBG trait in the pedigree is consonant with transmission by a dominant gene. A number of methods of evaluating serum thyroxine binding that are carried out under physiologic conditions of pH and thyroxine concentration have been compared with electrophoretically determined TBG and TBPA levels, and the findings are discussed in relation to the physiologic role of the 2 binding proteins.

Hyperthyroidism and decreased thyroxine binding by serum proteins.

In 2 sisters, hyperthyroidism was associated with normal levels of serum protein-bound iodine (PBI). A decrease in thyroxine (T4) binding by serum alpha-globulin (TBG) and pre-albumin (TBPA) was demonstrated in both cases by paper electrophoresis in ammonium carbonate buffer. TBG capacities were 0.08 and 0.11 μg. of T4 per ml., and the serum PBI levels were 5.1 and 6.6 μg. per 100 ml., respectively. TBG capacity among normal subjects ranged from 0.13 to 0.25 μg. of T4 per ml. The reduction in the TBG level is offered as the most likely explanation for the normal concentration of serum PBI in these patients. In one of the cases, repeated studies following radioiodine therapy revealed an increase in TBG and TBPA levels to low-normal and a fall in PBI concentration to an average value of 4.0 μg. per 100 ml. Chromatographic anatysis of the serum I131 compounds showed a normal ratio of T4 to T3. An incidental finding in both patients was the presence in the serum of an iodinated protein comprising nearly one-s...