EBM Consult

Lab Test: Total T4 or Thyroxine (Serum) Level

    Lab Test
    • Total T4 or Thyroxine (Serum)
    • Measurement of total thyroxine (T4) that is bound to plasma protein called thyroxine binding globulin in the serum for evaluation of thyroid gland function. 
    • Used to monitor thyroid replacement and/or suppressive therapy.
    Reference Range
    • Adults: 
      • Total T4 or Thyroxine = 4.5 - 10.9 mcg/dL (58 - 140 nmol/L)
    • Critical Values (Total T4): 
      • Newborn:  < 7 mcg/dL
      • Adult:  < 2 mcg/dL where myxedema coma is possible and if > 20 mcg/dL then thyroid storm possible
    • Free T4:
        • 0 - 4 days = 2 - 6 ng/dL (26 - 77 pmol/L)
        • 2 weeks to 20 years = 0.8 - 2 ng/dL (10 - 26 pmol/L)
        • Adult = 0.80 - 2.8 ng/dL (10 - 36 pmol/L)
    Indications & Uses
    • Hypothyroidism:
      • T4 (thyroxine) levels will be low  
      • Newborns are screened using total T4 tests to detect hypothyroidism.  A heel stick is used to collect the blood.  Mental impairment can be prevented with early diagnosis.
    • Hyperthyroidism:
      • T4 (thyroxine) levels will be high or elevated
    • Suspected subacute thyroiditis:
      • T4 (thyroxine) levels are usually elevated at presentation, then fall to normal as symptoms resolve. 
      • Increased T4 levels are found at presentation in 76% to 88% of patients.
      • In the late phase of subacute thyroiditis, the T4 level falls and may be low if colloid reserves are depleted.
    Clinical Application

    • Thyroid hormones (T4 and T3) are produced when tyrosine incorporates organic iodine to form monoiodotyrosine.  This complex picks up iodine and becomes diiodotyrosine.  
    • Two diiodotyrosines combine to for tetraiodothyronine (also called T4 thyroid hormone or thyroxine).  
    • If a diiodotyrosine combines with a monoiodotyrosine, triodothyronine (also called T3 thyroid hormone is formed.  
    • T4 makes up nearly 90% of what we call thyroid hormone.  
    • Nearly all of T4 and T3 is bound to protein called, thyroxine binding globulin.  Total T4 measurement consists of both the bound and unbound fractions.  
    • Thyroid hormones regulate a number of developmental metabolic, and neural activities throughout the body.  Abnormalities in protein levels can have a significant effect on the results of the total T4.  The combination of T4 and other thyroid function test results plus clinical findings is vital in the management of the patient with thyroid disease.  
    • Conditions that affect thyroxine-binding globulin levels may cause misleading results in total thyroxine measurement.  
      • Increased levels may indicate: 
        • Primary hyperthyroid states (e.g., Graves disease, Plummer disease, toxic thyroid adenoma), acute thyroiditis, familial dysalbuminemic hyperthyroxinemia, facitious hyperthyroidism, Struma ovarii, or TBG increase (e.g., as occurs in pregnancy, hepatitis, congenital hyperproteinemia).  
      • Decreased levels may indicate: 
        • Hypothyroid states (e.g., cretinism, surgical ablation, myxedema), pituitary insufficiency, hypothalamic failure, protein malnutrition and other protein-depleted states (e.g., nephrotic syndrome), iodine insufficiency, or non-thyroid illnesses (e.g., renal failure, Cushing disease, cirrhosis, surgery, advanced cancer)

    Related Tests
    • Thyroid panel
    • Transplant panel
    • Thyroid-stimulating immunoglobulins
      • Used to support the diagnosis of Graves disease, especially when the diagnosis is complete.
    • Thyrotropin-releasing hormone
      • Assists in the evaluation of patients with hyperthyroidism and hypothyroidism.  
      • It is especially helpful in the differential diagnosis of hypothyroidism. 
    • Thyroid-stimulating hormone
      • Used to diagnose primary hypothyroidism and to differentiate it from secondary (pituitary) and tertiary (hypothalamus) hypothyroidism. 
    • Thyroxine-binding globulin
      • A measure of TBG, the major thyroid hormone protein carrier.  
      • Used in the evaluation of patients who have abnormal total T4 and T3 levels.  
      • When performed concurrently with a T4/T3 test, the T4 and T3 levels can be more easily interpreted.
    • Triodothyronine (T3)
      • T3 is used to evaluate thyroid function.  
      • It is primarily used to diagnose hyperthyroidism. 
      • It is also used to monitor thyroid replacement and suppressive therapy. 
    • Antithyroglobulin antibody
      • Used in the differential diagnosis of thyroid diseases, such as Hasimoto thyroiditis and chronic lymphocytic thyroiditis (in children).
    Drug-Lab Interactions
    • Neonates have higher free T4 levels than older children and adults.
    • Prior use of iodinated radioisotopes or iodinated contrast can alter test results.
    • Pregnancy causes increased total T4 levels.
    • Drugs that increase free T4 levels include:  aspirin, danazol, heparin, and propranolol.
    • Drugs that decrease free T4 levels include:  furosemide, methadone, phenytoins, and rifampicin. 
    • Exogenously administered thyroxine causes increased free T4 results. 
    • Drugs that may cause increased total T4 levels include clofibrate, estrogens, heroin, methadone, and oral contraceptives. 
    • Drugs that may cause decreased T4 levels include:  anabolic steroids, androgens, antithyroid drugs (e.g., propylthiouracil), lithium, phenytoin, and propranolol.
    Test Tube Needed
    • Red top tube
    • Collect venous blood sample.
    • Follow the following steps for newborns:
      • Perform a hell stick to obtain blood.
      • Thoroughly saturate the circles on the filter paper with blood.
    • Note that prompt collection and processing are crucial to the early detection of hypothyroidism.
    • Apply pressure to the venipuncture site.
    Storage and Handling
    • Refrigerate specimen immediately.
    What To Tell Patient Before & After
    • Explain the procedure to the patient.
    • Evaluate the patient's medication history. 
    • If indicated, instruct the patient to stop exogenous T4 medication 1 month before testing. 
    • Tell the patient that no fasting is required. 
    • Explain to parents that newborns should be screened before discharge (regardless of age), because of the consequences of delayed diagnosis. 
    • Note that the optimal collection time is 2 to 4 days after birth.
    • Dayan CM.  Lancet 2001;357(9256):619-624.
    • Dofour DR.  Endocrinol Metab Clin of North Am 2007;36(3):579-594.
    • LaGow B et al., eds. PDR Lab Advisor. A Comprehensive Point-of-Care Guide for Over 600 Lab Tests.  First ed. Montvale, NJ: Thomson PDR; 2007.
    • Pagana K, Pagana TJ eds. Mosby's Manual of Diagnostic and Laboratory Tests. 5th Ed.  St. Louis, Missouri. 2014.

MESH Terms & Keywords

  • T4, Thyroxine, Thyroid Function, Hypothyroidism, Hyperthyroidism