Chemically blocked analog assays for free thyronines. I. The effect of chemical blockers on T4 analog and T4 binding by albumin and by thyroxin-binding globulin.

Analog assays for free thyroxin (FT4) produce inaccurate results because the T4 analog is sequestered by albumin. Diagnostic Products Corp. (DPC) introduced the concept of chemically blocking analog-albumin binding in 1982. While DPC succeeded in eliminating albumin dependence, their 1985 version of chemically blocked FT4 assay appeared to be "thyroxin-binding globulin" (TBG) dependent, producing inappropriately low FT4 results with low TBG concentrations and high results with high TBG concentrations. We examined the effects of chemical blockers on albumin and TBG binding, using equilibrium dialysis to measure free fractions of T4 analog and T4. We then created FT4 assays in which various concentrations of chemical blockers were used to demonstrate their effects on FT4 estimates in patients with low or increased TBG concentrations or who were pregnant. We found that chemical blockers do displace T4 analog from albumin, but also displace T4 from albumin and, in high concentrations, from TBG as well. It is this displacement of T4 from TBG by chemical blockers that resulted in "TBG dependence" of DPC FT4 estimates. This problem has been corrected in currently available versions of the DPC FT4 kit.