Thyroxine (T4)

Thyroxine (T4)

CPT Test code: 84436

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Specimen: Serum
Volume: 1 mL (adult), 0.8 mL (pediatric)
Minimum Volume: 0.5 mL (adult), 0.3 mL (pediatric) (Note: This volume does not allow for repeat testing.)
Container: Red-top tube or gel-barrier tube
Collection: If a red-top tube is used, transfer separated serum to a plastic transport tube.
Storage Instructions: Refrigerate
Reference Interval: 4.5-12.0 μg/dL1,2
Use: Thyroid function test. Decreased in hypothyroidism and in the third stage of (painful) subacute thyroiditis; increased with hyperthyroidism, with subacute thyroiditis in its first stage and with thyrotoxicosis due to Hashimoto disease.3 Used to diagnose T4 toxicosis.
Limitations: T4 may be increased with excess intake of iodine or with surreptitious use of thyroxine.3 T4 levels may be abnormal in the presence of systemic nonthyroidal disease. Alterations in binding capacity or quantity of TBG may increase or decrease total thyroxine without causing symptoms. A common cause of elevated T4 in nonthyroidal disease is said to be liver disease. Serum thyroxine and free thyroxine index (FTI) are increased in familial dysalbuminemic hyperthyroxinemia, a euthyroid syndrome in which an abnormal binding site has affinity for thyroxine.4 The T3 is usually normal in this entity, as is T3 uptake (THBR). Thus, T3 uptake is commonly ordered with T4.
Additional Information: The combination of the serum T4 and T3 uptake (THBR) as an indirect assessment of TBG, helps to determine whether an abnormal T4 value is due to alterations in serum thyroxine-binding globulin or to changes of thyroid hormone levels. Deviations of both tests in the same direction usually indicate that an abnormal T4 is due to abnormalities in thyroid hormone. Deviations of the two tests in opposite directions provide evidence that an abnormal T4 may relate to alterations in TBG.

Causes of increased TBG binding include neonatal state, molar and conventional pregnancy, estrogens, oral contraceptives, heroin, methadone, 5-fluorouracil, clofibrate, infectious hepatitis, chronic active hepatitis, and primary biliary cirrhosis, acute intermittent porphyria, lymphoma, and hereditary TBG increase.

Amphetamines, iopanoic acid, ipodate, and amiodarone increase thyroxine.5,6 High dose propranolol may elevate T4 and FTI levels.7

Causes of decreased TBG binding include abnormal protein states especially nephrotic syndrome, androgens, anabolic steroids, prednisone, acromegaly, liver or other systemic illness, severe stress or hereditary TBG deficiency. Salicylates and diphenylhydantoin may lower T4 significantly. Amiodarone may cause increased thyroxine levels and can cause hypothyroidism or hyperthyroidism.

Lithium carbonate may cause goiter with or without hypothyroidism.

Carbamazepine (Tegretol®) is reported to cause decreased values in thyroid function tests.

Footnotes: 1. Soldin SJ, Hicks JM, eds, Pediatric Reference Ranges, Washington, DC: AACC Press, 1995, 141.

2. Murthy JN, Hicks JM, Soldin SJ, “Evaluation of the Technicon Immuno I Random Access Immunoassay Analyzer and Calculation of Pediatric Reference Ranges for Endocrine Tests, T-Uptake, and Ferritin,” Clin Biochem, 1995, 28(2):181-5. PubMed 7628078

3. Klein I, Levey GS, “Silent Thyrotoxic Thyroiditis,” Ann Intern Med, 1982, 96(2):242-4. PubMed 7059071

4. Ruiz M, Rajatanavin R, Young RA, et al, “Familial Dysalbuminemic Hyperthyroxinemia: A Syndrome That Can Be Confused With Thyrotoxicosis,” N Engl J Med, 1982, 306(11):635-9. PubMed 6173750

5. Borst GC, Eil C, Burman KD, “Euthyroid Hyperthyroxinemia,” Ann Intern Med, 1983, 98(3):366-78. PubMed 6187257

6. Chopra IJ, Hershman JM, Pardridge MD, et al, “Thyroid Function in Nonthyroidal Illnesses,” Ann Intern Med, 1983, 98(6):946-57 (review). PubMed 6407376

7. Cooper DS, Daniels GH, Ladenson PW, et al, “Hyperthyroxinemia in Patients Treated With High-Dose Propranolol,” Am J Med, 1982, 73(6):867-71.PubMed 6816067

References: Franklyn JA, Davis JR, Ramsden DB, et al, “Phenytoin and Thyroid Hormone Action,” J Endocrinol, 1985, 104(2):201-4. PubMed 3918137

Gharib H, Klee GG, “Familial Euthyroid Hyperthyroxinemia Secondary to Pituitary and Peripheral Resistance to Thyroid Hormones,” Mayo Clin Proc, 1985, 60(1):9-15. PubMed 2981377

Gruhn JG, Barsano CP, and Kumar Y, “The Development of Tests of Thyroid Function,” Arch Pathol Lab Med, 1987, 111(1):84-100. PubMed 3541847

Surks MI, Chopra IJ, Mariash CN, et al, “American Thyroid Association Guidelines for the Use of Laboratory Tests in Thyroid Disorders,” JAMA, 1990, 263(11):1529-32.PubMed 2308185