Effect of chloride on serum thyroxine binding in familial dysalbuminemic hyperthyroxinemia

Chloride ion is known to inhibit the T4-albumin interaction in normal serum. To determine the extent of this effect on T4 binding to albumin in patients with familial dysalbuminemic hyperthyroxinemia (FDH), the serum percent free T4 (FT4) was measured by equilibrium dialysis in 0.1 M phosphate buffer, pH 7.4, and in phosphate buffer with 0.14 M NaCl (phosphate-saline buffer) in patients with FDH, normal subjects, and women in the third trimester of pregnancy, who served as a population with high serum T4-binding globulin concentrations. The FT4 was calculated as the product of the percent FT4 and total T4 concentration. The mean values of serum FT4 were similar among the three groups when equilibrium dialysis was performed in phosphate buffer. When the assay was carried out in phosphate-saline buffer, the mean percent FT4 in each group was higher than that obtained in phosphate buffer, resulting in higher mean serum FT4 concentrations. However, the mean serum FT4 in normal subjects and pregnant women remained similar. The increase in percent FT4 in phosphate-saline buffer was proportionally greater in the patients with FDH, and therefore the mean serum FT4 in these patients was significantly higher than that of normal subjects when phosphate-saline buffer was used (2.67 +/- 0.07 (SE) vs. 1.80 +/- 0.09 ng/dl, P less than 0.001), and all FT4 values were above the normal range. It is concluded that chloride ion inhibits serum T4 binding in patients with FDH more than it does in normal subjects, perhaps due to the fact that albumin plays a much greater role in overall T4 binding in these patients.