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Unit Code 8859:
T4 (Thyroxine), Free by Dialysis, Serum

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Useful For

Determining thyroid status of sick, hospitalized patients

 

Used where abnormal binding proteins are known to exist

 

Possibly useful in pediatric patients

Clinical Information

Thyroxine (T4) and triiodothyronine (T3) are the 2 biologically

active thyroid hormones. T4 makes up more than 80% of

circulating thyroid hormones.

 

Following secretion by the thyroid gland, approximately 70% of

circulating T4 and T3 are bound to thyroid-binding globulin

TBG), while 10% to 20% each are bound to  transthyretin (TTR) and

albumin, respectively. Less than 0.1% circulate as free T4 (FT4)

or free T3 (FT3). FT4 and FT3 enter and leave cells freely by

diffusion. Only the free hormones are biologically active, but

bound and free fractions are in equilibrium. Equilibrium with TTR

and albumin is rapid. By contrast, TBG binds thyroid hormones

very tightly and equilibrium dissociation is slow. Biologically,

TBG-bound thyroid hormone serves as a hormone-reservoir and

T4 serves as a prohormone for T3. Within cells, T4 is either

converted to T3, which is about 5 times as potent as T4, or reverse

T3, which is biologically inactive. Ultimately, T3, and to a much

lesser degree T4, bind to the nuclear thyroid hormone receptor,

altering gene expression patterns in a tissue-specific fashion.

 

Under normal physiologic conditions, FT4 and FT3 exert direct

and indirect negative feedback on pituitary thyrotropin (thyroid

stimulating hormone [TSH]) levels, the major hormone regulating

thyroid gland activity. This results in tight regulation of thyroid

hormone production and constant levels of FT4 and FT3

independent of the binding protein concentration. Measurement

of FT4 and FT3, in conjunction with TSH measurement therefore

represents the best method to determine thyroid function status.

It also allows determination of whether hyperthyroidism

(increased FT4) or hypothyroidism (low FT4) are primary

(the majority of cases, TSH altered in the opposite direction

as FT4) or secondary/tertiary (hypothalamic/pituitary origin,

TSH altered in the same direction as FT4). By contrast, total

T4 and T3 levels can vary widely as a response to changes

in binding protein levels, without any change in free thyroid

hormone levels and, hence, actual thyroid function status.

 

FT4 is usually measured by automated analog immunoassays.

In most instances, this will result in accurate results. However,

abnormal types or quantities of binding proteins found in some

patients and most often related to other illnesses or drug

treatments, may interfere in the accurate measurement of FT4

by analog immunoassays. These problems can be overcome

by measuring FT4 by equilibrium dialysis, free from interfering

proteins.

Reference Values

0.8-2.0 ng/dL

 

Reference values apply to all ages.

Interpretation

All free hormone assays should be combined with TSH

measurements.

 

FT4 <0.8 ng/dL indicates possible hypothyroidism.

FT4 >2.0 ng/dL indicates possible hyperthyroidism.

 

Neonates can have significantly higher FT4 levels. The

hypothalamic-pituitary-thyroid axis can take several days or,

sometimes, weeks to mature.

Cautions

Certain drugs may cause short-term FT4 fluctuations.

- Heparin

- Salicylates

     - Acetyl salicylic acid (aspirin)

     - Salicylic acid (salsalate)

- Furosemide

- Fenclofenac

- Mefenamic acid

- Flufenamic acid

- Diclofenac

- Difunisal

- Phenytoin

- Carbamazepine

 

The routine FT4 test (#8725 "T4 [Thyroxine], Free, Serum") is

faster and provides useful information in most patients.

Clinical Reference

1. De Brabandere VI, Hou P, Stockl D, et al:  Isotope dilution-liquid

     chromatography/electrospray ionization-tandem mass spectrometry

     for the determination of serum thyroxine as a potential reference

     method. Rapid Commun Mass Spectrom 1998;12:1099-1103

 

2. Jain R, Uy HL:  Increase in serum free thyroxine levels related to

     intravenous heparin treatment. Ann Intern Med 1996 Jan 1;124:74-75

 

3. Stockigt JR:  Free thyroid hormone measurement. A critical appraisal.

     Clin Endocrinol Metab 2001 Jun;30:265-289

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