Synonym

• Free T₄
• T4 Free
• FT₄
• Unbound T₄

Tubes

• Red or tiger top tube
• 5-7 mL of venous blood

Additional information

• Handle sample gently to prevent hemolysis
• Reject Lipemic or hemolyzed specimen
• Send the sample to lab immediately
• If being used to monitor thyroid replacement; typically a steady state will be present within 3-4 weeks after a dose change

Info

• The Free Thyroxine (FT₄) test measures the concentration of unbound, and thus metabolically active, thyroxine in the blood
• Thyroxine is a hormone secreted by the thyroid gland in response to TSH secreted by the pituitary gland in the brain. This hormone has metabolic and endocrine functions throughout the body. The rate of secretion is normally regulated by a system of negative and positive feedback mechanisms.
• About 0.05% of the total T₄ circulates freely in blood and the rest are bound strongly to plasma proteins, such as thyroxine binding globulin (TBG)
• Levels of free T₄ are proportional to levels of total T₄ and are normally inversely proportional to TSH

Clinical

• The Free Thyroxine (FT₄) test is used to evaluate for hyper or hypothyroidism, or to monitor therapy in treatment of either of these conditions
• In cases where screening for thyroid dysfunction, the TSH test is usually the only test necessary
• The clinical utility of FT₄ levels include:
• Measurement of the metabolically active thyroid hormone
• Aid in the diagnosis of hyperthyroidism and hypothyroidism
• Monitoring of therapeutic efficacy and disease progression in hyperthyroidism and hypothyroidism
• FT₄ concentration is a more accurate indicator of thyrometabolic activity, as it is not affected by fluctuations in TBG (unlike total T₄)
• Hyperthyroid state may be clinically seen as:
• General
• Anxious, restless, and fidgeting patient
• Exercise intolerance
• Fatigue
• Frequent bowel movements, diarrhea
• Goiter (Grave's disease)
• Heat intolerance
• Oligomenorrhea or amenorrhea
• Weight loss
• Cardiovascular
• Atrial fibrillation
• Cardiac hypertrophy
• Palpitations
• Systolic hypertension
• Systolic murmur (usually flow murmur)
• Tachycardia
• Wide pulse pressure
• Dermatologic
• Excessive sweating
• Hair is fine and silky
• Hair loss
• Finger nails may show onycholysis or brown discoloration
• Myxedema (Pre-tibial)
• Palmar erythema
• Warm, moist and velvety
• Eye
• Diplopia (Grave's disease)
• Exophthalmos (Grave's disease)
• Infrequent blinking
• Lid lag/Stare
• Periorbital edema
• Widened palpebral fissures
• Neuromuscular
• Hyperkinesia
• Proximal muscle weakness
• Rapid speech
• Tremor (fine usually, of tongue, fingers)
• Hypothyroid state may be clinically seen as
• General
• Cold intolerance
• Depression
• Edema; non-pitting to pre-tibial areas
• Face, round puffy or other facial edema (79%)
• Hypothermia (Usually mild)
• Loss of energy, lethargy
• Macroglossia (82%)
• Periorbital or eyelid edema (90%)
• Weight gain
• Voice; deep/husky
• Cardiovascular
• Bradycardia
• Cardiac enlargement
• Increased diastolic and decreased systolic blood pressure
• Indistinct heart tones
• Pericardial effusion
• Dermatologic
• Cold, dry, thick scaling skin affecting palms, soles, elbows and knees
• Dry, coarse, brittle hair (76%)
• Dry longitudinally ridged nails
• Hair loss (Axillary, pubic, scalp)
• Myxedema (non-pitting edema; most evident in infraorbital, pretibial, hand regions)
• Skin may show orange-yellow discoloration
• Gastrointestinal
• Constipation
• Ascites
• Menstrual disturbances, impaired fertility
• Neuropsychiatric
• Deep tendon reflexes delayed
• Flat affect and facial expression
• Generalized muscle weakness
• Hypokinesia
• Slow, clumsy body movements
• Slow speech
• In severe cases, coma and respiratory failure may occur

Additional information

• Normal day to day variation is about 15%
• Higher in winter and lower in summer
• Higher in men than in women
• Decreases with age (>55 yrs)
• Increased in infants at birth and rise even higher after 2–3 days of life
• Levels can fluctuate in patients with severe or chronic illness
• The methodologies used to measure the free T4 hormone levels include:
• Direct measurement of free T₄
• Equilibrium dialysis
• The gold standard in measuring free T₄ levels
• Disadvantages are that it is time-consuming, expensive, technically demanding, and unavailable in most commercial laboratories
• Immunoassays
• False higher levels in patients on levothyroxine therapy
• Indirect estimation of free T₄ (influenced by binding proteins or substances in serum)
• Two-step and one-step immunoassay methods using a T₄ analog
• Ultrafiltration method
• Factors interfering with the test results include:
• Lipid lowering agent containing D-T₄
• Auto-antibodies to thyroid hormones
• Related laboratory tests include:
• Antithyroglobulin and antithyroid peroxidase antibodies
• Free T₃
• T₃
• T₄
• Thyroid-binding inhibitory immunoglobulin
• Thyroid-stimulating immunoglobulin
• TSH

Nl Result

Consult your laboratory for their normal ranges as these may vary somewhat from the ones listed below.

* Newborns may have transient increased FT₄ levels in the first 4-5 days of life due to TSH release after birth; this is however not typically seen in premature infants.

High Result

Conditions associated with elevated free T₄ levels include:

• Euthyroid sick syndrome
• Fasting
• Gestational trophoblasticdisease
• Graves' disease (hyperthyroidism)
• Hyperemesis gravidarum
• Hypothyroidism over treated with thyroid hormone
• Jod-Basedow (iodine-induced )hyperthyroidism
• Lymphoma
• Pituitary adenoma/tumor (Increased TSH release)
• Postoperatively
• Pregnancy - first trimester
• Thyroid cancer
• Thyroiditis (Acute)
• Thyroid storm
• Toxic adenoma
• Toxic multinodular goiter
• Transient hyperthyroidism
• Subacute thyroiditis
• Hashimotos thyroiditis
• Postpartum period
• Drugs
• Acetylsalicylic acid (Aspirin)
• Aspirin
• Amiodarone
• Carbamazepine
• Danazole
• Enoxaparin
• Erythropoietin
• Furosemide
• Halofenate
• Heparin
• Iopanoic acid
• Iodinated dyes (Radiocontrast agents)
• Levothyroxine
• Phenytoin
• Propranolol
• Propylthiouracil
• T₄
• Tamoxifen
• Thyroid hormone replacement

Factors causing false high values of free T₄ levels include:

• Phenytoin and carbamazepine produce falsely increased results with analog immunoassays
• In virtually all assays, including equilibrium dialysis, results are falsely elevated (with room temperature incubation) in patients with decreased TBG or acute illness

Low Result

Conditions associated with decreased free T₄ levels include:

• Primary hypothyroidism
• Hashimotos thyroiditis
• Idiopathic myxedema
• Previous treatment of hyperthyroidism
• Subacute thyroiditis
• Prior neck radiotherapy
• Iodine deficiency or excess
• Congenital
• Secondary hypothyroidism (pituitary)
• Pituitary dysfunction (Low TSH)
• Tertiary hypothyroidism (hypothalamic)
• Hypothalamic disease (Low TRH)
• Addison's disease (30% patients)
• Cushing's syndrome
• Hemodialysis
• Hypothyroidism inadequately treated
• Severe low albumin level
• Severe Thyroxine-binding globulin decrease
• Congenital
• Disease state
• Drug induced
• Third trimester of pregnancy
• Tissue resistance to thyroid hormone (Very rare)
• Drugs
• Amiodarone
• Anabolic steroids
• Asparaginase
• Clofibrate
• Colestipol
• Corticosteroids
• Desipramine
• Diphenylhydantoin
• Estrogen therapy
• Isotretinoin
• Levothyroxine
• Lithium
• Mestranol
• Methadone
• Methimazole
• Nitroprusside
• Norethindrone
• Octreotide
• Oral contraceptives
• PAS
• Phenobarbital
• Phenylbutazone
• Ranitidine
• Rifampin
• Salsalate
• Thiourea
• Trimethoprim
• Sulfamethoxazole
• Valproic acid

References

• eMedicine from WebMD®. Hyperthyroidism. [Homepage on the Internet] ©1996-2006. Last updated on July 26, 2006. Last accessed on November 28, 2006. Available at URL: http://www.emedicine.com/PED/topic1099.htm
• eMedicine from WebMD®. Hypothyroidism. [Homepage on the Internet] ©1996-2006. Last updated on September 23, 2006. Last accessed on November 28, 2006. Available at URL: http://www.emedicine.com/MED/topic1145.htm
• Hoshikawa S et al. Artifactually elevated serum-free thyroxine levels measured by equilibrium dialysis in a pregnant woman with familial dysalbuminemic hyperthyroxinemia. Thyroid. 2004 Feb;14(2):155-60.
• Katsuhiko Y et al. Low free thyroxine concentrations and deficient nocturnal surge of thyroid-stimulating hormone in haemodialysed patients compared with undialysed patients. Nephrol Dial Transplant. (2000)15:668-672
• Laboratory Corporation of America®. Thyroxin (t4) Free, Direct, Serum. [Homepage on the internet]©2003. Last updated on October 26, 2006. Last accessed on November 23, 2006. Available at URL: http://www.labcorp.com/datasets/labcorp/html/chapter/mono/ri010200.htm
• Nelson JC et al. The nature of analogue-based free thyroxine estimates. Thyroid. 2004;14(12):1030-6.
• Palma Sisto PA. Endocrine disorders in the neonate. Pediatr Clin North Am. 2004;51(4):1141-68
• Sapin R et al. [Thyroxine (T4) and tri-iodothyronine (T3) determinations: techniques and value in the assessment of thyroid function] [Article in French]. Ann Biol Clin (Paris). 2003;61:411-20.
• Steele BW et al. Analytic bias of thyroid function tests: analysis of a College of American Pathologists fresh frozen serum pool by 3900 clinical laboratories. Arch Pathol Lab Med. 2005;129:310-7.
• Tran HA. Difficulties in diagnosing and managing coexisting primary hypothyroidism and resistance to thyroid hormone. Endocr Pract. 2006 May-Jun;12(3):288-93.
• UTMB Laboratory Survival Guide®. FREE THYROXINE. [Homepage on the Internet]© 2006. Last reviewed in February 2006. Last accessed on November 21, 2006. Available at URL: http://www.utmb.edu/lsg/LabSurvivalGuide/chem/FREE_THYROXINE.htm
• Vieira JG et al. [Free thyroxine values during pregnancy] [Article in Portuguese]. Arg Bras Endocrinol Metabol. 2004 Apr;48(2):305-9. Epub 2004 Jul 7.