Thyroxine 

Reference ranges for total thyroxine (TT4) are as follows[1, 2] :

• In newborns up to age 14 days: 11.8-22.6 mcg/dL (152-292 nmol/L)

• In babies and older children: 6.4-13.3 mcg/dL (83-172 nmol/L)

• In adults: 5.4-11.5 mcg/dL (57-148 nmol/L)

Reference ranges for free thyroxine (FT4) are as follows:

• In children/adolescents: 0.8-2 ng/dL (10-26 pmol/L)

• In adults: 0.7-1.8 ng/dL (9-23 pmol/L)

• In pregnant patients: 0.5-1 ng/dL (6.5-13 pmol/L)

Normal value ranges may vary among different laboratories.

SI conversion: pmol/L = 12.9 x ng/dL

Conditions and circumstances associated with changes in thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and FT4 levels are listed in table 1, below.

Table 1* ^{[3, 4, 5]} (Open Table in a new window)

*Table adapted from: Dayan CM. Interpretation of thyroid function tests. Lancet. 2001 Feb 24. 357 (9256):619-24.

**Goitrogen - Any substance that interferes with iodine uptake in the thyroid gland, thereby decreasing production of thyroid hormones.

The following conditions are associated only with TT4 values that are higher than normal:

• High levels of the protein that carries T4 in the blood, mainly, thyroxine-binding globulin (TBG), which could be acquired, such as in pregnancy, use of birth control pills (oral contraceptives) or estrogen, liver disease, or as part of an inherited condition

• Altered affinity of other thyroxine-binding proteins such as albumin and prealbumin (transthyretin)

The following conditions are associated only with TT4 values that are lower than normal:

• Low levels of the protein that carries T4 in the blood, mainly TBG, which can be congenital or acquired (eg, corticosteroid or androgen use)

No special preparations are needed for this test. However, certain medications may affect the test result, including seizure medications, cardiac drugs, steroids, birth control pills, and even aspirin.[9]

The following drugs/supplements can increase TT4 measurements:

• Birth control pills

• Clofibrate

• Estrogens

• Methadone[10]

• Biotin[11]

The following drugs can decrease TT4 measurements:

• Anabolic steroids

• Androgens

• Antithyroid drugs (propylthiouracil, methimazole)

• Interferon alfa[7]

• Interleukin-2

• Lithium

• Phenytoin

• Propranolol

For specimen preparation, usually 1 mL of blood serum is collected by venipuncture (in adults) or by heel stick (in newborns) and drawn in a red-top container.

The following are related tests:

• TSH

• T3

• Antithyroid antibodies

Description

T4 is one of two major hormones produced by the thyroid gland; the other is T3. T4 makes up about 90% of thyroid hormones. A feedback mechanism maintains thyroid hormone at an appropriate level in the body. When the level of T4 in the bloodstream decreases, the hypothalamus releases TSH-releasing hormone (TRH), which stimulates the pituitary gland to release TSH, which, in turn, stimulates the thyroid gland to make and/or release more T4 and T3. As blood concentrations of T4 increase, TSH release is inhibited.

In the blood, T4 is either free (not bound) or protein-bound (primarily bound to TBG). The concentration of FT4 is only about 0.1% that of TT4. T4 is converted into T3 in the liver and other tissues. T3, like T4, is also highly protein bound. It is the free forms of T3 and T4 that are biologically active. FT3 is 4-5 times more active than FT4.

One of the thyroid hormones' principal functions is to stimulate the consumption of oxygen and, thus, the metabolism of all cells and tissues in the body.

The chemical structure of T4 is shown below.

Thyroxine structural formula.

Indications/applications

Indications for T4 testing include the following[5] :

• After finding an abnormal TSH level

• To confirm the diagnosis of thyroid disorders (hyperthyroidism and hypothyroidism)

• To monitor the appropriateness of thyroid replacement therapy

• To screen for the presence of an underactive thyroid gland in newborn babies

• When a person has symptoms of hyperthyroidism or hypothyroidism and pituitary/hypothalamic involvement is suspected (secondary/tertiary hyperthyroidism or hypothyroidism)

Signs and symptoms of hyperthyroidism may include the following[12] :

• Increased heart rate

• Anxiety

• Weight loss

• Difficulty sleeping

• Tremors in the hands

• Weakness

• Diarrhea (sometimes)

• Light sensitivity, visual disturbances

• Heat intolerance

• Increased perspiration

• Menstrual irregularity

• Eye symptoms, possibly including puffiness around the eyes, dryness, irritation, and, in some cases, bulging of the eyes

• Infertility[13]

Signs and symptoms of hypothyroidism may include the following:

• Weight gain

• Dry skin

• Constipation

• Cold intolerance

• Puffy skin

• Hair loss

• Fatigue

• Menstrual irregularity

• Cognitive dysfunction, including depression

• Joint and/or muscle aches

Considerations

TT4 and FT4 are two separate tests that can help to evaluate thyroid function.

The TT4 test has been used in the past to help diagnose hyperthyroidism and hypothyroidism. It is a useful test but can be affected by the amount and affinity of protein available in the blood to bind to the hormone. The FT4 test is a newer test that is usually not affected by protein levels. Since FT4 is the active form of T4, the FT4 test is thought by many to be a more accurate reflection of thyroid hormone function, and, in most cases, its use has replaced that of the TT4 test.

The following medications and situations may preclude performing the test (TT4) or may render the test results not useful:

• Corticosteroids, estrogen, progesterone, or birth control pills

• Blood-thinning medicines such as acetylsalicylic acid (ASA; aspirin), heparin, or warfarin (Coumadin)

• Antiseizure medicines such as phenytoin (Dilantin) or carbamazepine (Tegretol)[14]

• Heart medicines such as amiodarone or propranolol[6]

• Lithium

• Biotin supplements[11]

• Recent history of having had an imaging study, such as a computed tomography (CT) scan, that uses contrast material

• Pregnancy