Dependence of the thyroxin/thyroxin-binding globulin (TBG) ratio and the free thyroxin index on TBG concentrations.

We studied the dependence of the free thyroxin (T4) index and the ratio of T4 to thyroxin-binding globulin (TBG) on TBG concentrations, using sera from cases of congenital TBG deficiency and congenital TBG excess. Two such sera with similar concentrations of albumin, transthyretin, and free T4 were mixed to provide test samples with TBG concentrations covering the range of clinical interest without changes in the other T4-binding proteins. Total T4, free T4, TBG, triiodothyronine (T3) uptake, and the free fraction of T3 in serum were measured, and we calculated the free T4 indices, T4/TBG ratios, and the free fraction of T4. A 100-fold variation in TBG concentration was associated with a 10-fold variation in total T4, a fourfold variation in T3 uptake, and a 10-fold variation in the T4/TBG ratio. As TBG concentrations increased, the T4/TBG ratio decreased and the free T4 index increased. The free T4 index did not parallel the T4/TBG ratio, and neither the T4/TBG ratio nor the free T4 index reflected the concentrations of free T4 in serum.