Junta Takamatsu

Two new inherited defects of the thyroxine-binding globulin (TBG) molecule presenting as partial TBG deficiency.

Serum-denatured TBG (dnTBG) measured in 32 families deficient in native TBG (nTBG) was undetectable in all subjects with complete nTBG deficiency and was high in 2 of 16 families with partial nTBG deficiency. nTBG (in mean micrograms per decaliter +/- SD) in members of the Quebec and Montreal families, respectively were: 258 +/- 54 and 230 in affected men, 747 +/- 190 and 927 +/- 90 in affected women, and 1568 +/- 151 and 1300 +/- 195 in unaffected relatives. Corresponding mean dnTBG levels were: 14.3 +/- 2.9 and 21.3 in affected men, 8.6 +/- 1.0 and 11.6 +/- 3.1 in affected women, and less than 2.1 and less than 2.6 in unaffected relatives. All were euthyroid with normal free thyroxine and thyrotropin levels. In comparison to common type TBG, TBG-Quebec was more heat labile by 10 degrees C and TBG-Montreal by 12 degrees C. The degree of dnTBG elevation and nTBG lability at 37 degrees C were correlated (r = 0.99). Isoelectric focusing showed cathodal shift of all TBG bands: TBG-Quebec by 0.06 isoelectric points (pI) and TBG-Montreal by 0.02 pI. These two TBG variants represent different mutations most likely affecting the polypeptide chain of the molecule. Their inheritance is X-chromosome linked. The instability of these TBGs at 37 degrees C may lead to more rapid degradation in vivo resulting in low nTBG and high dnTBG concentrations in serum.

Inherited Abnormality of Thyroxine-Binding Globulin with No Demonstrable Thyroxine-Binding Activity and High Serum Levels of Denatured Thyroxine-Binding Globulin

THYROID hormones (thyroxine and triiodothyronine) are transported in blood bound to serum proteins.1 2 3 The principal protein, which carries approximately 75 percent of the total thyroxine and tri...

A New Form of X-Chromosome Linked TBG Abnormality with No Demonstrable T4-Binding Activity

Diagnostic work-up for short stature uncovered TBG deficiency in an 11 year old girl (propositus) with XO Turner’s syndrome. Studies on members of the family revealed that the two hemizygous affected subjects (propositus and father) had, compared to the mean normal levels, 1.5% native (n) TBG and 9-fold to 10-fold increased denatured (dn) TBG, both measured by specific RIAs. The heterozygous sister had 30% nTBG and 5.6-fold increased dnTBG, while the mother had normal levels (Table 1).

Thyroid Function Tests in Subjects with a Genetic Isoelectric Focusing Variant TBG

A variant thyroxine-binding globulin (TBG) with slower migration on isoelectric focusing (TBG-S) has been found in some American Blacks. It is inherited as an X-chromosome-linked trait. Hemizygous males with TBGS exhibit TBG bands shifted cathodally. Heterozygous females with TBG-CS, show the summation pattern of TBG bands corresponding to sera from subjects with only TBG-S and those with only the common type of TBG (TBG-C). Because the effect of TBG-S on thyroid function has not been studied in detail, we compared data of thyroid function tests in sex and age matched subjects belonging to four TBG genotypes (10 males each with TBG-S vs. TBG-C, and 10 females each with TBG-CS vs. TBG-CC). The mean serum T4 level of the group of males with TBG-S was 6.79 + 1.52 (SD) μg/dl, significantly lower than that of the group of males with TBG-C (8.49 + 1.29 lig/μl, p<0.02). A significant concomitant reduction in the mean serum TBG concentration was found in the group of males with TBG-S as compared to that with TBG-C (1.41 + 0.30 mg/dl vs. 1.72 + 0.29 mg/dl, p<0.05). Mean values of serum free T4 concentrations and other tests of thyroid function, including TSH levels, were not significantly different among the four groups matched by age and paired by sex. Although the reason for the reduced serum TBG concentration in subjects with TBG-S remains unclear the associated reduction of serum T4 levels is not accompanied by hypothyroidism.