For the differential diagnosis of euthyroid hyperthyroxinemia from hyperthyroidism or for the differential diagnosis of euthyroid hypothyroxinemia from hypothyroidism.

This test may be useful in assessing thyroid dysfunction when pituitary disease is not suspected. In patients with clinical suspicion of hyperthyroidism or hypothyroidism, testing thyroid stimulating hormone (TSH) is the initial step [1]. An abnormal TSH result will reflex to a free thyroxine (T4) test to aid in diagnosis and guide further testing if needed.

TSH stimulates the thyroid gland to synthesize and secrete triiodothyronine (T3) and T4. TSH production is reduced in response to high T3/T4 levels and increased in response to low T3/T4 levels. When pituitary disease is not suspected, TSH serves as a sensitive marker for screening for thyroid dysfunction [1,2]. A normal TSH result excludes most cases of primary overt thyroid disease. When the TSH level is elevated, measurement of free T4 level may help diagnose subclinical or overt hypothyroidism. Thyroid peroxidase antibody testing may be needed to aid in the diagnosis of Hashimoto thyroiditis. When the TSH level is decreased, measurement of free T4 and free T3 may help identify hyperthyroidism or T3 thyrotoxicosis. In patients with thyrotoxicosis, TSH receptor antibodies testing helps confirm Graves disease [1-3].

Note: Interference due to heterophile antibodies has been known to occur [1].

The results of this test should be interpreted in the context of pertinent clinical and family history and physical examination findings.

References
1. Demers LM, et al. The thyroid: pathophysiology and thyroid function testing. In: Burtis CA, et al. eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 4th ed. Elsevier; 2006:2053-2095.
2. Ross DS, et al. Thyroid. 2016;26(10):1343-1421.
3. Vasileiou M, et al; Guideline Committee. BMJ. 2020;368:m41.

Total T₃ measurements are used to diagnose and monitor treatment of hyperthyroidism and are essential for recognizing T₃ toxicosis.

Graves' disease is a classic form of hyperthyroid disease, affecting approximately 0.4% of the population of the United States. It is caused by IgG immunoglobulins, collectively known as thyroid stimulating immunoglobulins (TSI). Patients who are candidates for antithyroid drug therapy may not respond to this treatment when TSI levels are markedly elevated. The determination of TSI can also assist in predicting hyperthyroidism in neonates, due to placental transmission of the immunoglobulins from a mother with hyperthyroidism.

The Thyroid Cascading Reflex order code that will act as an aid to physicians in the diagnosis of common adult thyroid disorders. The initial results of a TSH will determine further reflex orders of T₄, Free, TPO Antibodies and T₃, Free orders and provided an interpretation based upon the results of the reflexed tests.

For differential diagnosis of primary, secondary, and tertiary hypothyroidism. Also useful in screening for hyperthyroidism. This assay allows adjustment of exogenous thyroxine dosage in hypothyroid patients and in patients on suppressive thyroxine therapy for thyroid neoplasia.

The T4 Free (FT4) test measures serum thyroxine (T4) that is not bound to thyroid hormone-binding proteins (thyroid hormone-binding globulin [TBG], transthyretin, albumin) and is thus readily available to target cells. This test is used with thyroid-stimulating hormone measurement (TSH, test code 899) in the diagnosis of hyperthyroidism (usually displaying elevated FT4) and hypothyroidism (low FT4), including congenital and acquired hypothyroidism.

The FT4 test is used to assess thyroid function, monitor thyroid conditions, and assess treatment effectiveness. It has largely replaced the total T4 test (test code 867), which measures both bound and free T4, because the FT4 test is less affected by levels of thyroid hormone-binding proteins.

This test uses a T4 analog, rather than equilibrium dialysis, to determine the amount of free T4. It therefore differs from the T4 Free, Direct Dialysis test (test code 35167). In the general population, the analog FT4 test is most useful as a follow-up test when TSH results are abnormal. It may also be used instead of TSH testing to assess thyroid function in patients with (1) known pituitary abnormalities; (2) chronically suppressed TSH, as often seen in patients for months after successful treatment for Graves disease [1]; or (3) a need to assess thyroid hormone dose changes sooner than the 6-8 weeks required for TSH to reach a new stable level. When the levels of thyroid hormone-binding proteins are very abnormal (eg, congenital TBG deficiency or excess; preterm infants [2]) or the affinity of binding proteins is altered [3] (eg, familial dysalbuminemic hyperthyroxinemia), the T4 Free, Direct Dialysis test will provide more accurate results.

References
1. Ross DS. N Engl J Med 2011;364:542-550.
2. Deming DD et al. J Pediatr. 2007;151:404-408.
3. Refetoff S. Abnormal Thyroid Hormone Transport. [Updated 2015 Jul 15]. In: Feingold KR, Anawalt B, Boyce A, et al, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000.