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Second-order testing for hyperthyroidism in patients with low thyroid-stimulating hormone values and normal thyroxine levels
Diagnosis of triiodothyronine toxicosis
Thyroid hormones regulate a number of developmental, metabolic, and neural activities throughout the body. The thyroid gland synthesizes 2 hormones: The 2 main hormones secreted by the thyroid gland are thyroxine, which contains 4 atoms of iodine (T4), and triiodothyronine (T3). T3 production in the thyroid gland constitutes approximately 20% of the total T3; the rest is generated by the conversion (deiodination) of T4 to T3 is also produced by conversion (deiodination) of T4 in peripheral tissues. Circulating levels of T4 are much greater than T3 levels, but T3 is biologically the most metabolically active hormone (3-4 times more potent than T4) although its effect is briefer due to its shorter half-life compared to T4.
Thyroid hormones circulate primarily bound to carrier proteins (eg, thyroid-binding globulin [TBG], prealbumin and albumin); whereas only a small fraction circulates unbound (free). The free form of T3 is the biologically active fraction. Only the free forms are metabolically active. While both T3 and T4 are bound to TBG, T3 is bound less firmly than T4. Total T3 consists of both the bound and unbound fractions.
In hyperthyroidism, both T4 and T3 levels are usually elevated, but in a small subset of hyperthyroid patients only T3 is elevated (T3 toxicosis).
In hypothyroidism T4 and T3 levels are decreased. T3 levels are frequently low in sick or hospitalized euthyroid patients.
See Thyroid Function Ordering Algorithm in Special Instructions.
Adult (> or =20 years): 80-200 ng/dL
0-5 days: 73-288 ng/dL
6 days-2 months: 80-275 ng/dL
3-11 months: 86-265 ng/dL
1-5 years: 92-248 ng/dL
6-10 years: 93-231 ng/dL
11-19 years: 91-218 ng/dL
Triiodothyronine (T3) values >200 ng/dL in adults or > age related cutoffs in children are consistent with hyperthyroidism or increased thyroid hormone-binding proteins.
Abnormal levels (high or low) of thyroid hormone-binding proteins (primarily albumin and thyroid-binding globulin) may cause abnormal T3 concentrations in euthyroid patients.
Triiodothyronine (T3) is not a reliable marker for hypothyroidism.
T3 is not useful for general screening of the population without a clinical suspicion of hyperthyroidism. Therapy with amiodarone can lead to depressed T3 values.
Phenytoin, phenylbutazone, and salicylates cause release of T3 from the binding proteins, thus leading to a reduction in the total T3 hormone level at normal free T3 levels.
Autoantibodies to thyroid hormones can interfere with the assay.
Binding protein anomalies may cause values which deviate from the expected results. Pathological concentrations of binding proteins can lead to results outside the reference range, although the patient may be in a euthyroid state. Free T3 or free T4 testing is indicated in these cases.
Some patients who have been exposed to animal antigens, either in the environment or as part of treatment or imaging procedures, may have circulating antianimal antibodies present. These antibodies may interfere with the assay reagents to produce unreliable results.
In patients receiving therapy with high biotin doses (ie, >5 mg/day), no sample should be taken until at least 8 hours after the last biotin administration.
1. Hay ID, Klee GG: Linking medical needs and performance goals: clinical and laboratory perspectives on thyroid disease. Clin Chem 1993;39:1519-1524
2. Klee GG: Clinical usage recommendations and analytic performance goals for total and free triiodothyronine measurements. Clin Chem 1996;42:155-159