Measured vs. calculated free T4.

Q Most automated chemistry analyzers now can directly determine free T4 (fT4). What are the advantages and disadvantages of replacing a calculated a free thyroxine index (FTI) with a directly determined free T4. I find much of what I read confusing because it seems authors, sometimes, will not clearly state whether they are talking about FTI or directly determined free T4.

A The FTI has been replaced in most cases by a free T4 measurement because it tends to be less susceptible to abnormal results at the extremes of measurement of the total T4 or the T3 resin binding (the two assays that make up the calculated FTI).

Most thyroidologists no longer use the FTI except in unusual cases (non-thyroidal illness, for one example, because of circulating endogenous inhibitors that can affect fT4 assays). The one other common scenario where a total T4 may be preferred to an fT4 is during pregnancy, with a correction factor for the increased thyroid binding globulin (TBG) levels, but this is controversial. Outside of these examples, FTI is less and less frequently ordered.

In turn, fT4 assays can be done a number of ways, most commonly by analog methods. These can also be susceptible to assay interference. The "gold standard" fT4 assay is direct equilibrium dialysis, which we measure when we get confusing results from the analog assays.

--Mary Samuels, MD

Professor of Medicine

Oregon Health and Science University

Portland, OR