Thyroxine, Free (FT4)

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Subject: Thyroxine, Free (FT4)

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Definition

  • Both free and bound forms of T4 and T3 are present in the blood. More than 99% of the T4 and T3 circulates in the blood bound to carrier proteins, leaving <1% unbound. It is this level of unbound or free hormone that correlates with the functional thyroid state in most individuals. FT4 is usually 0.02–0.04% of total T4 (see Table 16.76).

  • Normal range (adults): 0.58–1.64 ng/dL.

    • Pregnant women:

      • First trimester: 0.73–1.13 ng/dL

      • Second trimester: 0.54–1.18 ng/dL

      • Third trimester: 0.56–1.09 ng/dL

Use

  • FT4 gives corrected values in patients in whom the total T4 is altered on account of changes in serum proteins or in binding sites (e.g., pregnancy, drugs [such as androgens, estrogens, birth control pills, phenytoin], altered levels of serum proteins [e.g., nephrosis]).

  • Monitoring restoration to normal range is the only laboratory criterion to estimate appropriate replacement dose of levothyroxine because 6–8 weeks are required before TSH reflects these changes.

  • Not generally helpful unless pituitary/hypothalamic disease is suspected.

Interpretation

Increased In

  • Hyperthyroidism.

  • Hypothyroidism treated with thyroxine.

  • Euthyroid sick syndrome.

  • Occasional patients with hydatidiform mole or choriocarcinoma with marked hCG elevations may show increased FT4, suppressed TSH, and blunted TSH response to TRH stimulation; returns to normal with effective treatment of trophoblastic disease; severe dehydration (may be >6.0 ng/dL).

Decreased In

  • Hypothyroidism

  • Hypothyroidism treated with triiodothyronine

  • Euthyroid sick syndrome

Limitations

  • FT4 assays based on direct equilibrium dialysis are considered reference methods.

  • FT4 assays are prone to inaccurate readings in pregnant women. The studies have shown that FT4 index measurement is more reliable than free T4 immunoassays in pregnant women.

  • Anticonvulsant drug therapy (particularly phenytoin) may result in decreased FT4 levels due to an increased hepatic metabolism and secondarily to displacement of hormone from binding sites.

 
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