As an estimate the amount of circulating free T4, when in conjunction

with total T4 results to calculate the free thyroxine index (FTI)

Thyroxine (T4) is the main thyroid hormone. It circulates in 2 forms,

protein-bound (99.05%) and free (0.05%). Free thyroxine (FT4) is

the biologically active form. Both bound and free forms are

measured by total T4 (TT4) assays. While TT4 is a relatively

reliable indicator of T4 levels in the presence of normal binding

proteins, it is not a reliable indicator when binding proteins are

abnormal. For example, increases in thyroxine-binding proteins

may cause increased TT4 levels despite normal FT4 levels

and normal thyroid function. Hence, laboratory tests have been

developed to compensate for the presence of abnormal types

or quantities of thyroxine-binding proteins. These include the

T-Uptake test (also called T3 uptake), the free thyroxine index

FTI), and FT4 assays.

The T-Uptake test reflects the level of thyroid-binding globulin

(TBG) that is bound by T4. For example, when TBG concentration

is decreased, less TBG is available to bind labeled triiodothyronine

(T3), and more labeled T3 reagent binds to the solid-phase material

(increased T3 uptake). This is also the case in hyperthyroidism,

where higher levels of T4 are present and bind with the TBG,

effectively reducing TBGs availability to bind with labeled T3.

T-Uptake and TT4 results are used to calculate the FTI, as an

estimate of biologically active thyroxine (FT4) status:

Factors affecting the accuracy of T-Uptake and FTI include:

            - FTI is inaccurate when TBG concentration is very abnormal:

              under-estimates FT4 when binding protein concentrations

              are low, overestimates when binding protein concentrations

              are high.

            - Abnormal types of binding proteins may cause abnormal results.

            - Results are changed by drugs or physical conditions that alter

              the patient's TBG levels, or drugs that compete with endogenous

              T4 and T3 for protein-binding sites.

Because of its increased accuracy, the FT4 assay (#200050 T4 [Thyroxine],

Free, Serum by immunoassay) is the preferred routine test.

Males:  27-37%

Females:  20-37%

The T-Uptake values used are interpreted in conjunction with

total T4 measurements.

FTI=T4 concentration x % T-Uptake/100

The FTI is a normalized determination that

remains relatively constant in healthy individuals and

compensates for abnormal levels of binding proteins.

Hyperthyroidism causes increased FTI and hypothyroidism

causes decreased values.

Many drugs, by competing with endogenous T4 and T3 for

protein-binding sites, may cause abnormal T-Uptake and

FTI even when no thyroid malfunction is present. Physical

conditions that alter TBG levels may have similar effects

(see Cautions).

T-Uptake values are a function of thyroid hormone binding capacity

of serum.

Conditions that decrease T-Uptake values:

      -  Conditions that decrease T-Uptake values:

             -  Pregnancy (especially in the last trimester)

             -  Elevated estrogen levels

             -  Acute hepatitis

             -  Drugs which prevent ovulation

      -  Conditions that elevate T-Uptake values:

             -  Protein malnutrition

             -  Chronic liver disease

             -  Nephrotic syndrome

             -  Phenytoin therapy

             -  Heparin therapy

             -  Uremia

             -  Large doses of salicylates

             -  Antibiotics

Thyroid preparations that maintain normal T3 and T4 concentrations

can elevate T-Uptake values when the hormone dose is excessive

and decrease T-Uptake values when the dose is inadequate.

Replacement therapy with T3 results in decreased

T-Uptake values.

1.   Whitley RJ, Meikle AW, Watts NB:  Thyroid Function. In Tietz

     Fundamentals of Clinical Chemistry.  Fourth edition.  Edited by CA

     Burtis, ER Ashwood.  Philadelphia, EB Saunders Company, 1996,

     pp 645-646

2.   Klee GG, Hinz VS: The Ciba Corning ACS:180 Plus. In Immunoassay

     Automation: An Updated Guide to Systems.  Edited by DW Chan,

Associated Press, New York, 1996, pp 63-102