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Thyroxine 

  • Author: Muhammad Bader Hammami, MD; Chief Editor: Eric B Staros, MD  more...
 
Updated: Jul 23, 2013
 

Reference Range

Reference ranges for total thyroxine (TT4) are as follows:

  • 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

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Interpretation

The following conditions can be associated with thyroxine (T4) (total thyroxine [TT4], free thyroxine [FT4]) values that are higher than normal:

  • Graves disease
  • Toxic multinodular goiter
  • Toxic thyroid adenoma
  • Subacute thyroiditis
  • Silent (painless) thyroiditis
  • Iodine-induced hyperthyroidism
  • Trophoblastic disease secreting human chorionic gonadotropin
  • Germ cell tumors secreting human chorionic gonadotropin
  • Amiodarone (drug effect)

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 can be associated with T4 (TT4, FT4) values that are lower than normal:

  • Hypothyroidism (including Hashimoto disease, thyroidectomy, use of antithyroid drugs and lithium)
  • Amiodarone (drug effect)
  • Congenital hypothyroidism
  • Iodine deficiency
  • Nonthyroid illness
  • Malnutrition or fasting

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 use)
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Collection and Panels

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

The following drugs can increase total thyroxine (TT4) measurements:

  • Birth control pills
  • Clofibrate
  • Estrogens
  • Methadone

The following drugs can decrease total thyroxine (TT4) measurements:

  • Anabolic steroids
  • Androgens
  • Antithyroid drugs (propylthiouracil ,methimazole)
  • Interferon alfa
  • 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:

  • Thyroid-stimulating hormone (TSH)
  • Triiodothyronine (T3)
  • Antithyroid antibodies
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Background

Description

Thyroxine (T4) is 1 of 2 major hormones produced by the thyroid gland; the other is called triiodothyronine (T3). T4 makes up about 90% of thyroid hormones. When the body requires thyroid hormone, the thyroid gland releases stored T4 into circulation under the regulation of thyroid-stimulating hormone (TSH) released from the pituitary gland, which, in turn, is regulated by TSH-releasing hormone (TRH), which is released from the hypothalamus.

In the blood, T4 is either free (not bound) or protein-bound (primarily bound to thyroxine-binding globulin). The concentration of free T4 is only about 0.1% of that of total T4. 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. Free T3 is 4-5 times more active than free T4.

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 body has a feedback system that turns thyroid hormone production on and off. When the level of T4 in the bloodstream decreases, the hypothalamus releases 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.

The chemical structure of thyroxine is shown below.

Thyroxine structural formula. Thyroxine structural formula.

Indications/applications

Indications for T4 testing include the following:

  • 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 under-active 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:

  • Increased heart rate
  • Anxiety
  • Weight loss
  • Difficulty sleeping
  • Tremors in the hands
  • Weakness
  • Diarrhea (sometimes)
  • Light sensitivity, visual disturbances
  • Eye symptoms, possibly including puffiness around the eyes, dryness, irritation, and, in some cases, bulging of the eyes

Signs and symptoms of hypothyroidism may include the following:

  • Weight gain
  • Dry skin
  • Constipation
  • Cold intolerance
  • Puffy skin
  • Hair loss
  • Fatigue
  • Menstrual irregularity in women

Considerations

Total T4 (TT4) and free T4 (FT4) are 2 separate tests that can help 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 thyroxin, 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)
  • Heart medicines such as amiodarone or propranolol
  • Lithium
  • Recent history of having had an x-ray test that uses contrast material
  • Pregnancy
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Contributor Information and Disclosures
Author

Muhammad Bader Hammami, MD Resident Physician, Department of Internal Medicine, St Louis University School of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital

Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology

Disclosure: Nothing to disclose.

References
  1. Chernecky CC, Berger BJ. Laboratory Tests and Diagnostic Procedures. 5th ed. Philadelphia, Pa: Elsevier Saunders; 2008.

  2. Fischbach FT, Dunning MB III, eds. Manual of Laboratory and Diagnostic Tests. 8th ed. Philadelphia, Pa: Lippincott Williams and Wilkins; 2009.

  3. Kaplan MM. Clinical perspectives in the diagnosis of thyroid disease. Clin Chem. 1999 Aug. 45(8 Pt 2):1377-83. [Medline].

  4. Kratz A, Ferraro M, Sluss PM, Lewandrowski KB. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Laboratory reference values. N Engl J Med. 2004 Oct 7. 351(15):1548-63. [Medline].

  5. Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology. 12th ed. Philadelphia, Pa: Saunders Elsevier; 2011. Chapter 11.

  6. Tietz NW, ed. Clinical Guide to Laboratory Tests. 3rd ed. Philadelphia, Pa: WB Saunders; 1995.

 
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Thyroxine structural formula.
 
 
 
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