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Test Code FRT4D T4 (Thyroxine), Free by Dialysis, Serum

Reporting Name

T4 (Thyroxine), Free by Dialysis, S

Useful For

Determining thyroid status of sick, hospitalized patients

 

Used where abnormal binding proteins are known to exist

 

Possibly useful in pediatric patients

Method Name

Equilibrium Dialysis/Tandem Mass Spectrometry (MS/MS)

Performing Laboratory

Mayo Medical Laboratories in Rochester

Specimen Type

Serum


Specimen Required


Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 2.6 mL

Collection Instructions: Serum must be separated from gel within 4 to 6 hours of draw.

Additional Information: Include name and telephone number of contact physician.


Specimen Minimum Volume

1.2 mL

Specimen Stability Information

Specimen Type Temperature Time
Serum Refrigerated (preferred) 28 days
  Frozen  21 days
  Ambient  7 days

Reject Due To

Hemolysis

Mild OK; Gross reject

Lipemia

Mild OK; Gross reject

Icterus

Mild OK; Gross OK

Other

NA

Reference Values

0.8-2.0 ng/dL

Reference values apply to all ages.

Day(s) and Time(s) Performed

Monday, Wednesday, Thursday; 3 p.m.

CPT Code Information

84439 

LOINC Code Information

Test ID Test Order Name Order LOINC Value
FRT4D T4 (Thyroxine), Free by Dialysis, S 6892-4

 

Result ID Test Result Name Result LOINC Value
8859 T4 (Thyroxine), Free by Dialysis, S 6892-4

Analytic Time

3 days

Cautions

The routine free thyroxine (FT4) test (FRT4 / T4 [Thyroxine], Free, Serum) is faster and provides useful information in most patients.

 

Certain drugs may cause short-term FT4 fluctuations.

-Heparin

-Salicylates

  - Acetylsalicylic acid (aspirin)

  - Salicylic acid (salsalate)

-Furosemide

-Fenclofenac

-Mefenamic acid

-Flufenamic acid

-Diclofenac

-Diflunisal

-Phenytoin

-Carbamazepine

Method Description

The equilibrium dialysis method separates free thyroxine (FT4) from serum proteins and, thereby, also from protein-bound thyroxine (T4), before measuring it in the protein-free dialysate using sensitive, tandem mass spectrometry. The results are independent of the concentrations of the T4-binding proteins and unaffected by the presence of molecular variants of these proteins.(Soldin SJ, Soukhova N, Janicic N, et al: The measurement of free thyroxine by isotope dilution tandem mass spectrometry. Clin Chim Acta 2005 Aug;358:113-118)

Interpretation

All free hormone assays should be combined with thyroid-stimulating hormone measurements.

 

Free thyroxine (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.

Specimen Retention Time

2 weeks

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

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% circulates 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.