Free Thyroxine Index Variants
Last Updated: 2020-06-10 (1 year ago)
Author: David Baorto, MD, PhD
Date Written: January 2012
Although direct measurement of the free hormones has recently become more prevalent, the older methods to estimate free hormone levels by deriving an index still persist. The index methods involve adjusting the total thyroid hormone concentration (TT4) for the thyroid binding capacity of the serum (T3 uptake or thyroid binding globulin TBG) to yield an indicator or estimate of the free hormone level, free thyroxine index (FTI). Over time and across labs this calculation has been and is done in different ways, yielding different results sometimes with different properties. This is mostly due to distinctions in what is known as “T uptake”. Here are some variations:
- FTI = TT4(ug/ml) x T3 uptake (%)/100
- This has sometimes been noted leaving off the division by 100, but not in practice: FTI = TT4(ug/ml) x T3 uptake(%).
- FTI = TT4(ug/ml) x (T3 uptake patient/T3 uptake control) (ratio)
- Here, “T3 uptake” used in the calculation is actually the thyroid hormone binding ratio noted throughout the literature (THBR), the ratio of patient to reference serum values of T3 uptake.
- FTI = TT4(ug/ml) / T uptake units (ratio)
- Here “T uptake units” is ratio of patient to reference serum levels of thyroxine binding globulin (TBG).
- In variation 1, the uptake is a %, while in variations 2 and 3 the uptake is a unit-less ratio normalized to control, known in the literature as the thyroid hormone binding ratio (THBR).
- Variation 1 is apparently the reporting approach used by Mayo, ARUP, and LabCorp and many hospital labs (such as one large NY hospital). It adjusts the total T4 by a T3 uptake % (approximate range 25-40%), and yields FTI values often in the approximate range of 1 to 5 (adults) and is reported as unit-less.
- Variation 2 is apparently the reporting approach used by Quest Diagnostics-Nichols and some hospital labs (such as another large NY hospital), and variation 3 apparently the primary method used by Abbott Axsym (although values can be converted).
- Variations 2 and 3 both adjust the total T4 (TT4) by a ratio referenced to a control value of 1, so FTI numerically is in the approximate range of TT4 concentration 5 – 12 (adults). While it is usually reported as unit-less, there is a case that it is really an adjusted TT4 concentration, and in fact the Abbott AxSym package insert (variation 3 above) notes units of ug/dl for its calculated FTI value.
- THBR is a normalized T3 uptake which represents how much labeled T3 did NOT find a binding site in patient serum, meaning it is the INVERSE of available binding sites. Conversely, in the AxSYM method “T uptake units” is a control normalized ratio of TBG, a measure proportional to the binding sites. This may account for why one MULTIPLIES and the other DIVIDES by the ratio. The TBG is not the only thyroid hormone binding protein, another distinction between 2 and 3.
- Historically T3 instead of T4 has been more commonly used as the tracer in uptake assays for practical reasons. T3 has a lower affinity for TBG, so more would be available to be taken up by the scavenger and easier to count. With non-isotopic techniques, this may be less of an issue, and it has been suggested that T4 uptake would be more appropriate to adjust TT4 concentration. T4 uptake assays do exist.