Normal cellular uptake of thyroxine from serum of patients with familial dysalbuminemic hyperthyroxinemia or elevated thyroxine-binding globulin.

To determine whether thyroid hormone-binding proteins in serum, particularly albumin, facilitate the transfer of T4 into human tissues, we studied cellular T4 uptake (CT4) by human liver (Hep G2) cells from medium containing serum from subjects with familial dysalbuminemic hyperthyroxinemia (FDH) and acquired and familial T4-binding globulin (TBG) excess and patients with normal T4-binding to albumin and normal TBG concentrations. Serum from nine subjects with FDH whose mean serum total T4 (TT4) concentration was 203 +/- 27 nmol/L were matched for TT4 concentrations with serum from nine subjects with acquired TBG excess (TT4, 201 +/- 23 nmol/L) and nine subjects with thyrotoxicosis and normal TBG concentrations (TT4, 205 +/- 28 nmol/L). The subjects' CT4 results were compared to their serum free T4 concentration, measured by equilibrium dialysis (DT4), and their serum free T4 index (FT4I) value. The mean serum DT4 value for the subjects with FDH (23 +/- 5 fmol/L) and those with TBG excess (23 +/- 3 fmol/L) were normal, whereas it was elevated (44 +/- 9 fmol/L; P less than 0.001) for the thyrotoxic patients with normal TBG concentrations. The mean CT4 value also was normal for the subjects with FDH (37.7 +/- 4.9 fmol/plate) and those with TBG excess (36.6 +/- 4.6 fmol/plate), but was elevated for the thyrotoxic patients (62.3 +/- 11.2 fmol/plate; P less than 0.001). In all three groups studied, the relationship between individual CT4 and DT4 values was similar to that previously found in subjects with no T4-binding protein abnormalities. The mean serum FT4I value was lower for the subjects with acquired TBG excess (111 +/- 22) than for the subjects with FDH (133 +/- 22; P less than 0.05), and it was much higher for the subjects with thyrotoxicosis (221 +/- 31; P less than 0.001). In the subjects with FDH and those with thyrotoxicosis the normal relationship between CT4 and FT4I was maintained, while in the subjects with acquired TBG excess, FT4I values were lower than expected. In seven of the nine subjects with TBG excess, the abnormality was associated with conditions known to increase its sialic acid content: hepatitis (one subject), pregnancy (four subjects), and estrogen therapy (two subjects). The CT4 values were similar in nine subjects with acquired TBG excess (seven pregnant women and two subjects with chronic active hepatitis) and five subjects with familial TBG excess (34.8 +/- 4.3 vs. 34.0 +/- 8.6 fmol/plate, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)