Free Thyroxine Index - Kresser Institute Membership Site

Marker Name: Free Thyroxine Index

REFERENCE RANGE FOR FREE THYROXINE INDEX:

Laboratory reference range: 1.2–4.9

DESCRIPTION:

The free thyroxine index (free T4 index; FTI; T7) is one of the tests used to estimate free thyroxine (T4) hormone levels.¹ Since FTI includes T3 resin uptake in its calculation, FTI can also “correct” or normalize total T4 values by accounting for potential abnormalities in thyroid hormone-binding protein levels in the serum.^1,2

FTI is calculated using the following equation:³

free-thyroxine-index

The FTI relies on two measured values: total T4 and T3 resin uptake. Total T4 is technically a measure of both bound and unbound T4 in the serum. However, approximately 99.98 percent of T4 in the serum is bound, so total T4 is effectively a measure of bound T4 and is unaffected by small differences in free T4 concentrations.¹ The T3 resin uptake test detects and quantifies potential binding protein abnormalities. T3 resin uptake is a complex marker that is directly proportional to the saturation of thyroid hormone molecules on serum-binding proteins.

When thyroxine-binding proteins are present in normal concentrations in the serum, an elevated FTI usually indicates hyperthyroidism, since FTI reflects free T4 levels. In T4 toxicosis, free T4 may be elevated without an associated increase in T3, though TSH will be abnormally low.⁴ This pattern of laboratory findings may also be present in individuals with hyperthyroidism and concurrent non-thyroidal illness, amiodarone-induced thyroid dysfunction, or exogenous estrogen.⁵ Uncommonly, an elevated free T4 (i.e., FTI) may be caused by a TSH-producing pituitary tumor. Increased levels of thyroxine-binding globulin (TBG), such as during a normal pregnancy, will elevate the FTI by increasing T3 resin uptake.³

Conversely, low free T4 levels in the context of normal TBG concentrations in serum usually indicate hypothyroidism. TBG-deficient individuals will also have a lower-than-normal FTI due to decreased T3 resin uptake. There are various reasons someone would be deficient in TBG, but these are usually due to decreased protein synthesis or increased protein excretion by the kidney.

Given that FTI is a calculation of measured values, it can only be determined from measurements of total T4 and T3 resin uptake. When FTI is reported, total T4 measurements are also provided, which is important for interpretation.¹ Clinical laboratories also provide the thyroid hormone-binding ratio or index (THBR or THBI) with FTI results.¹ FTI is also measured with other indices of thyroid function, such as thyroid-stimulating hormone (TSH), total T3, free T3, and reverse T3.

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:^1,6-8

Pregnancy
Hyperthyroidism
T4 toxicosis
Euthyroid hyperthyroxinemia
TSH-mediated hyperthyroidism
Acute thyroiditis
Familial dysalbuminemic hyperthyroxinemia
Drugs
- Drugs that increase TBG (e.g., estrogens, tamoxifen, opioids)
- Drugs that decrease T4 conversion to T3 (e.g., amiodarone)

Low in:^1,6,9

Hypothyroidism
Chronic thyroiditis
Subacute thyroiditis
Congenital thyroid agenesis, dysgenesis, or defects in hormone synthesis
Nephrosis
Drugs
- Synthetic triiodothyronine treatment
- Drugs that decrease TBG (e.g., anabolic steroids, glucocorticoids)
- Drugs that increase T4 clearance (e.g., phenytoin, carbamazepine, phenobarbital)
- Drugs that inhibit T4 synthesis/release (e.g., thionamides, lithium, perchlorate)

FUNCTIONAL RANGE INDICATIONS:

High in:

No functional range; same as conventional indications

Low in:

No functional range; same as conventional indications

References: