Measurement of thyroxine uptake from serum by cultured human hepatocytes as an index of thyroid status: reduced thyroxine uptake from serum of patients with nonthyroidal illness.

Abstract

The uptake of T4 from human serum by cultured human hepatoma cells, Hep G2, was compared with the free T4 estimates by equilibrium dialysis (DT4) and a resin uptake method (FT4I). The cellular uptake of T4 (CT4) was highly correlated with DT4 values (r = 0.97; P less than 0.0005) and FT4I values (r = 0.99; P less than 0.0005) in sera from euthyroid subjects and hypothyroid and thyrotoxic patients. In patients with abnormal levels of serum T4-binding globulin, the fractional uptake of T4 decreased as the TBG level increased, and the CT4 value remained within the normal range. Addition of increasing amounts of T4 to serum from a hypothyroid patient did not alter the relationships between CT4 and FT4I and between CT4 and DT4. DT4 and CT4 measurements were compared in sera from 13 patients with severe nonthyroidal illness (NTI). Six samples had DT4 values that clearly overestimated the cellular uptake, 2 patients had DT4 values in the thyrotoxic range but normal CT4 values, and 2 patients had DT4 values in the midnormal range and CT4 values below normal. When FT4I and CT4 values were compared in 19 NTI patients, 5 had FT4I values below the normal range and normal CT4 values. Overall, among patients with NTI, FT4I was low in 11 (58%), normal in 8 (42%), and high in 0; CT4 was low in 6 (32%), normal in 13 (68%), and high in 0, and DT4 was low in 2 (15%), normal in 9 (69%), and high in 2 (15%). In patients with NTI, the results of in vitro estimations of free T4 do not always correlate with the transfer of T4 to tissues, as assessed by T4 uptake in human hepatoma cells. In patients with NTI, equilibrium dialysis may overestimate and resin uptake measurements may underestimate the amount of T4 taken up by tissues. In some patients with severe NTI, tissue uptake of T4 is reduced.