Order Code
4273
Preferred Specimen
Collect 1 mL of serum. Allow the serum separator tube (SST) to clot while upright for a minimum of 30 minutes. Centrifuge the sample within 2 hours of collection. Store refrigerated.
ContainerType
Serum separator tube
Alternate Specimen Requirements
Obtain 2 mL of serum from a plain red top tube. Allow the sample to clot in an upright position for at least 60 minutes. Centrifuge and transfer the serum into a plastic transport tube within 2 hours of collection. Clearly label the tube as serum from a plain red top tube. Keep refrigerated.
Mnimum Volume
Adult: 0.5 mL serum
Pediatric: 0.2 mL serum (does not allow for repeat or
additional testing).
Transport Temperature
Refrigerated
Expected Turnaround Time
1-2 days
Specimen Stability
5 days room temperature; 1 week refrigerated; 1 month frozen. Allow only one freeze/thaw cycle
Methodology
Roche COBAS Electrochemiluminescent Immunoassay (ECLIA) method traceable to equilibrium dialysis ft3 method.
Overview
Triiodothyronine (T3), named for its three iodine atoms, is one of the two primary hormones secreted by the thyroid gland, alongside thyroxine (T4). Roughly 20% of circulating T3 is directly secreted by the thyroid, while the remaining 80% is generated through peripheral conversion of T4. In the bloodstream, T3 exists mostly bound to proteins (~99.7%) with a small fraction (~0.3%) circulating freely; only the unbound or free T3 is biologically active.
Measurement of T3 is particularly useful in assessing hyperthyroidism when thyroid-stimulating hormone (TSH) levels are suppressed but total or free T4 values are within normal limits. In such cases, elevated total or free T3 supports a diagnosis of T3 thyrotoxicosis, which accounts for approximately 5% of hyperthyroid presentations. While total T3 testing is more frequently ordered due to better validation, free T3 measurement is preferred when abnormal levels of carrier proteins may influence interpretation. Carrier proteins—including thyroxine binding globulin (TBG), prealbumin, and albumin—can be increased during pregnancy or decreased in states like malnutrition.
It should be noted that T3 (either free or total) is not reliable for evaluating hypothyroidism because it tends to be the last thyroid hormone to decline and may remain within normal limits even in severe hypothyroidism (AACE 2012).
Clinical Significance
- Evaluate suspected hyperthyroidism (especially T3 toxicosis or subclinical T3 hyperthyroidism) when blood protein levels may be reasonably anticipated to be abnormal (eg, pregnancy, malnutrition)
- Assess severity of diagnosed hyperthyroidism
- Supportive criteria for suspected nonthyroidal illness (also known as euthyroid sick syndrome) where T3 levels are typically low
- Monitor therapy (replacement or suppressive)
- Not recommended for routine thyroid function screening
- Not reliable in the evaluation of hypothyroidism
Additional Information
The thyroid gland is responsible for absorbing dietary iodine and converting it into the hormones thyroxine (T4) and triiodothyronine (T3). These hormones are released into circulation primarily bound to thyroxine binding globulin (TBG), with smaller amounts bound to thyroxine-binding prealbumin and albumin. Peripheral tissues and the liver convert T4 into the more biologically active T3, which binds to thyroid receptors in nearly all major organs involved in metabolism, including the heart, brain, liver, muscle, and skin. Both T4 and T3 regulate metabolic processes by altering gene expression, thereby influencing protein synthesis rates (Brent 2012).
Thyroid hormone production is regulated via a classical negative feedback loop involving the hypothalamus, pituitary gland, and thyroid. Reduced levels of T3 and T4 stimulate the hypothalamus to release thyrotropin-releasing hormone (TRH), which promotes the pituitary to secrete thyroid-stimulating hormone (TSH). This, in turn, stimulates thyroid production of T4 and T3. Conversely, elevated levels of T3 and T4 inhibit this axis, reducing hormone release.
Normal thyroid hormone output consists of about 80% T4 and 20% T3. Although T3 is approximately four times more potent than T4, its plasma concentration is roughly one-fortieth that of T4. Additionally, T3 has a shorter half-life of approximately 2.5 days compared to 6.5 days for T4 (Poduval 2015).
Interpretative Information
Decreased:
- Primary hypothyroidism (eg, Hashimoto thyroiditis)
- Central hypothyroidism (eg, pituitary dysfunction, tumors)
- Nonthyroidal illness (NTI) (otherwise known as euthyroid sick syndrome)
- After thyroidectomy or radioactive iodine (RAI) therapy for hyperthyroidism
- Antithyroid medication use (propylthiouracil, methimazole)
- Certain medications:
- Propranolol (suppresses conversion of T4 to T3)
- Amiodarone (inhibits deiodination of T4 to T3; may also cause destructive thyroiditis) (Loh 2000)
- Androgens/glucocorticoids (decrease conversion of T4 to T3)
- Lithium (inhibition of thyroid hormone synthesis and release, resulting in hypothyroidism in approximately 15% to 50% of patients)
- Phenobarbital, phenytoin, carbamazepine, rifampin (increase rate of clearance by increasing deiodination of T4 and T3)
Increased:
- Hyperthyroidism (eg, Graves disease, toxic multinodular or uninodular goiter, iodine-induced hyperthyroidism)
- T3 elevation seen in approximately 5% of hyperthyroidism
- T3 may be normal in the presence of isolated T4 thyrotoxicosis
- Acute thyroiditis
- Early during treatment with antithyroidal drugs (T3 may still be elevated)
- Relapse after treatment with antithyroidal drugs
- Excess thyroid replacement hormone
- Certain medications
- Amiodarone (37% iodine, causes amiodarone-induced thyrotoxicosis [AIT]) (Tsang 2009)
- Thyroxine and levothyroxine replacement therapy
Limitations
- Not reliable in evaluation of hypothyroidism as T3 remains normal in mild to moderate thyroid gland dysfunction, and even in severe hypothyroidism (high TSH, low T4), T3 may be within normal limits as it is the last thyroid hormone to decrease in concentration (AACE 2012)
- Levels of T3 may be uninterpretable in the presence of desiccated thyroid (made from dried animal thyroid glands) therapy which contains both T4 and T3
- Levels of T3 are challenging to interpret in the presence of T3 (Cytomel) therapy unless the time of administration is known due to T3’s short half-life and rapid rise to peak concentrations (Henry’s 2007)
- High circulating levels of biotin can interfere with thyroid function assays, most commonly causing falsely high levels of T3, free T3 and free T4 and falsely low levels of TSH, leading to an incorrect diagnosis of hyperthyroidism or conclusion that thyroid hormone dose is too high. Results inconsistent with clinical picture should be investigated (Li 2017).
References
Aytug S. Euthyroid sick syndrome. Medscape website. http://emedicine.medscape.com/article/118651-overview. Updated November 20, 2015. Accessed December 1, 2015.
Bahn RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract. 2011;17(3):456-520.21700562
Brent GA. Mechanisms of thyroid hormone action. J Clin Invest. 2012;122(9):3035-3043.22945636
Dayan CM. Interpretation of thyroid function tests. Lancet. 2001;357(9256):619-624.11558500
Ehrmann DA, Sarne DH. Serum thyrotropin and the assessment of thyroid status. Ann Intern Med. 1989;110(3):179-181.2643378
Galarza JB. Thyroid function tests. In: Farwell A, ed. Clinical Thyroidology for the Public. Falls Church, VA: American Thyroid Association; 2018:11(12):3-4. https://www.thyroid.org/wp-content/uploads/publications/ctfp/volume11/issue12/ct_public_v1112_3_4.pdf. Accessed July 22, 2020.
Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012;18(6):988-1028.23246686
Li D, Radulescu A, Shrestha RT, et al. Association of Biotin Ingestion With Performance of Hormone and Nonhormone Assays in Healthy Adults. JAMA. 2017;318(12):1150-1160. doi:10.1001/jama.2017.13705.28973622
Loh KC. Amiodarone-induced thyroid disorders: a clinical review. Postgrad Med J. 2000;76(893):133-140.10684321
Luong JHT, Vashist SK. Chemistry of Biotin-Streptavidin and the Growing Concern of an Emerging Biotin Interference in Clinical Immunoassays. ACS Omega. 2019;5(1):10-18.31956746
McPherson RA, Pincus MR, eds. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 3rd ed. Philadelphia PA: Saunders Elsevier; 2007.
Poduval J. Triiodothyronine. Medscape website. http://emedicine.medscape.com/article/2089598-overview. Updated January 17, 2014. Accessed December 1, 2015.
Spencer CA. Assay of thyroid hormones and related substances. In: De Groot LJ, ed. Thyroid Disease Manager [Internet]. South Dartmouth, MA: MDText.com, Inc.; 2000-2015. http://www.thyroidmanager.org/chapter/assay-of-thyroid-hormones-and-related-substances/. Updated January 1, 2013. Accessed December 2, 2015.
Supit EJ, Peiris AN. Interpretation of laboratory thyroid function tests for the primary care physician. South Med J. 2002;95(5):481-485.12005004
Tsang W, Houlden RL. Amiodarone-induced thyrotoxicosis: a review. Can J Cardiol. 2009;25(7):421-424.19584973
Umpierrez GE. Euthyroid sick syndrome. South Med J. 2002;95(5):506-513.12005007
Diagnostic Role
Free T3 levels are, in general, a second line test in the evaluation of thyroid disorders as they are less widely validated than tests for total T3. Free T3 levels, however, are indicated in those situations where binding protein quantities are likely to be abnormal (eg, pregnancy or malnutrition) or when the total T3 level is inconsistent with the clinical picture (AACE 2011).
Free T3 blood levels are primarily used in the evaluation of symptoms consistent with hyperthyroidism or to determine the severity of the hyperthyroidism in clinical situations with abnormal levels of binding proteins. Even so, free T3 is typically not the first test ordered, but is useful after TSH and T4 have been found to be abnormal or incongruous (eg, signs of hyperthyroidism, but normal T4 results). In approximately 5% of hyperthyroid cases, a low TSH is seen in the presence of normal T4 levels, and typically represents T3 thyrotoxicosis (AACE 2011). Free T3 (and free T4) levels are also indicated early in the post-treatment period of hyperthyroidism with antithyroid drugs, radioiodine, or surgery to ensure success of treatment, as the TSH level in the blood may remain subnormal for several weeks (Ehrmann 1989).
T3 blood levels (free or total) are rarely helpful in the evaluation of hypothyroidism as T3 is the last test to become abnormal. Patients can be even severely hypothyroid with a high TSH and low T4 levels, but still have a normal T3. It is important to note that the most reliable therapeutic endpoint for the treatment of primary hypothyroidism is the serum TSH value, not T3 or T4 levels (AACE 2012).
T3 levels (free or total) are not indicated when assessing the appropriateness of levothyroxine (T4) dosing in hypothyroidism as patients on T4 replacement therapy may have elevated blood T4 levels and lower T3 (free and total) levels. The correct test in this setting is the TSH level where a normal TSH indicates adequate thyroxine replacement (AACE 2012).
Alias
- free triiodothyronine (free t3)
- t3 (triiodothyronine) free
- triiodothyronine, free
Test Setup Days
Monday through Friday PM shift
CPT
84481 If Free T3 Is Measured, It Is Not Considered Appropriate To
Measure T3 Total.
Medicare Payment For T3 Total Will Be Denied If Ordered On
The Same Day As Measured Free T3.
LOINC: 3051-0
Reference Range
AGE 0-3 DAYS: 2.0-7.9 PG/ML
4 DAYS-1 MONTH: 2.0-5.2 PG/ML
1 MONTH-2 YEARS: 1.6-6.4 PG/ML
2-6 YEARS: 2.0-6.0 PG/ML
7-17 YEARS: 2.9-5.1 PG/ML
>=18 YEARS: 2.2-4.2 PG/ML
| UNIT CODE | UNIT CODE NAME | ANALYTE | GENDER | AGE | REFERENCE RANGE | Units of Measure |
|---|---|---|---|---|---|---|
| 4273 | FREE T3 | FT3 | NOT SPECIFIED | 0Y | 2.2-4.2 | PG/ML |
| 4273 | FREE T3 | FT3 | NOT SPECIFIED | 3D | 2.0-7.9 | PG/ML |
| 4273 | FREE T3 | FT3 | NOT SPECIFIED | 1M | 2.0-5.2 | PG/ML |
| 4273 | FREE T3 | FT3 | NOT SPECIFIED | 2Y | 1.6-6.4 | PG/ML |
| 4273 | FREE T3 | FT3 | NOT SPECIFIED | 6Y | 2.0-6.0 | PG/ML |
| 4273 | FREE T3 | FT3 | NOT SPECIFIED | 17Y | 2.9-5.1 | PG/ML |
| 4273 | FREE T3 | FT3 | NOT SPECIFIED | 150Y | 2.2-4.2 | PG/ML |
| 4273 | FREE T3 | FT3 | MALE | 0Y | 2.2-4.2 | PG/ML |
| 4273 | FREE T3 | FT3 | MALE | 3D | 2.0-7.9 | PG/ML |
| 4273 | FREE T3 | FT3 | MALE | 1M | 2.0-5.2 | PG/ML |
| 4273 | FREE T3 | FT3 | MALE | 2Y | 1.6-6.4 | PG/ML |
| 4273 | FREE T3 | FT3 | MALE | 6Y | 2.0-6.0 | PG/ML |
| 4273 | FREE T3 | FT3 | MALE | 17Y | 2.9-5.1 | PG/ML |
| 4273 | FREE T3 | FT3 | MALE | 150Y | 2.2-4.2 | PG/ML |
| 4273 | FREE T3 | FT3 | FEMALE | 0Y | 2.2-4.2 | PG/ML |
| 4273 | FREE T3 | FT3 | FEMALE | 3D | 2.0-7.9 | PG/ML |
| 4273 | FREE T3 | FT3 | FEMALE | 1M | 2.0-5.2 | PG/ML |
| 4273 | FREE T3 | FT3 | FEMALE | 2Y | 1.6-6.4 | PG/ML |
| 4273 | FREE T3 | FT3 | FEMALE | 6Y | 2.0-6.0 | PG/ML |
| 4273 | FREE T3 | FT3 | FEMALE | 17Y | 2.9-5.1 | PG/ML |
| 4273 | FREE T3 | FT3 | FEMALE | 150Y | 2.2-4.2 | PG/ML |