Thyroxine (T₄)

Serum (preferred) or plasma

1 mL (adult), 0.8 mL (pediatric)

0.7 mL (adult), 0.3 mL (pediatric) (Note: This volume does not allow for repeat testing.)

Red-top tube, gel-barrier tube, or green-top (lithium heparin) tube. Do not use oxalate, EDTA, or citrate plasma.

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.

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.

Electrochemiluminescence Immunoassay (ECLIA)

4.5−12.0 μg/dL^1,2

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.