Order Code
2818
Preferred Specimen
Collect 2 mL of serum.
Allow the serum separator tube (SST) to clot upright for at least 30 minutes, then centrifuge within 2 hours of collection. Store the specimen refrigerated.
ContainerType
Serum separator tube
Alternate Specimen Requirements
Submit 2 mL of serum from a plain red-top tube.
Allow the sample to clot upright for a minimum of 60 minutes, centrifuge, and then transfer the serum to a labeled plastic transport tube within 2 hours.
Clearly label the tube as “serum from plain red-top”. Store refrigerated.
Minimum Volume
Adult: 1 mL serum
Pediatric: 0.2 mL serum (does not allow for repeat or
additional testing).
Transport Temperature
Refrigerated
Expected Turnaround Time
1 day
Specimen Stability
8 days room temperature; 2 weeks refrigerated; 1 year frozen. Allow only one freeze/thaw cycle
Methodology
Roche COBAS Electrochemiluminescent Immunoassay (ECLIA)
Overview
Triiodothyronine (T3), named for its three iodine atoms, is one of the primary hormones produced by the thyroid gland—the other being thyroxine (T4). Roughly 20% of circulating T3 is secreted directly by the thyroid; the remaining 80% is generated through peripheral conversion of T4.
T3 and T4 levels are regulated through a hypothalamic-pituitary-thyroid (HPT) feedback loop. When T3 and T4 levels drop, the hypothalamus releases thyrotropin-releasing hormone (TRH), prompting the pituitary to secrete thyroid-stimulating hormone (TSH), which stimulates the thyroid to produce more T3 and T4. Elevated thyroid hormone levels suppress TRH and TSH production in turn.
The Total T3 test, the most commonly ordered T3 assay, measures both the protein-bound and free fractions of T3. Approximately 99.7% of T3 circulates bound to thyroxine-binding globulin (TBG), prealbumin, and albumin, with only 0.3% circulating in the free (active) form. T3 is more biologically active than T4.
Clinical Use
Total T3 measurement is particularly useful in the evaluation of hyperthyroidism, especially when TSH is suppressed but T4 remains within the normal range. In such cases, an elevated T3 level supports a diagnosis of T3 thyrotoxicosis, which accounts for approximately 5% of hyperthyroid presentations.
T3 is not a reliable marker for diagnosing hypothyroidism, as T3 levels tend to decline later in the disease course. Even in severe hypothyroidism, T3 may remain within the reference range (AACE, 2012).
Clinical Significance
- Evaluate suspected hyperthyroidism (especially T3 toxicosis or subclinical T3 hyperthyroidism).
- 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 synthesizes hormones by uptaking dietary iodine, which it converts into T4 and T3. These hormones circulate in the bloodstream predominantly bound to TBG, with additional binding to prealbumins and albumins. In peripheral tissues (e.g., liver, muscle, brain, heart, skin), T4 is converted to T3, which exerts metabolic effects by binding to nuclear thyroid hormone receptors and modulating gene expression (Brent, 2012).
The normal thyroid secretes approximately 80% T4 and 20% T3. While T3 is about four times more potent than T4, its serum concentration is roughly 1/40th that of T4. The half-life of T3 is 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)
- Recovering subacute thyroiditis
- Nonthyroidal illness (NTI) (otherwise known as euthyroid sick syndrome)
- After thyroidectomy or radioactive iodine (RAI) therapy for hyperthyroidism
- Antithyroid medication use (propylthiouracil, methimazole)
- Low serum protein levels (eg, malnutrition, nephrotic syndrome, chronic liver disease)
- 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
- Elevated serum protein levels (pregnancy, genetically increased TBG levels)
- 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)
- Estrogens
Limitations
- Abnormal blood protein levels (in particular, thyroxine binding globulin (TBG), prealbumin, albumin) affect T3 levels
- Falsely low T3 levels due to decreased protein levels from malnutrition, nephrotic syndrome, chronic liver disease, GI protein loss
- Falsely high T3 levels due to increased protein levels from pregnancy, oral birth control use, or genetically increased TBG (AACE 2012)
- 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
Baskin HJ, Cobin RH, Duick DS, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract. 2002;8(6):457-469.15260011
Bowen R, Benavides R, Colón-Franco JM, et al. Best practices in mitigating the risk of biotin interference with laboratory testing. Clin Biochem. 2019;74:1-11.31473202
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
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
Katzman BM, Lueke AJ, Donato LJ, Jaffe AS, Baumann NA. Prevalence of biotin supplement usage in outpatients and plasma biotin concentrations in patients presenting to the emergency department. Clin Biochem. 2018;60:11-16.30036510
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.2017.1370528973622
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
Wang D, Stapleton HM. Analysis of thyroid hormones in serum by liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem. 2010;397(5):1831-1839.20437035
Diagnostic Role
T3 blood levels are primarily used in the evaluation of symptoms consistent with hyperthyroidism or to determine the severity of the hyperthyroidism. T3 is typically not the first test ordered in this clinical situation, but is useful after TSH and T4 have been found to be abnormal or incongruous with the clinical situation (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). T3 blood levels 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).
Total T3 is the preferred test over free T3 as assays for free T3 are less widely validated; however, free T3 levels are preferred in those situations where binding proteins are likely to be abnormal (eg, pregnancy or malnutrition) or when the total T3 level is inconsistent with the clinical picture (AACE 2011).
Alias
- Total t3
- Triiodothyronine, total
Test Setup Days
Monday through Friday PM shift
CPT
84480 LOINC: 3053-6
Reference Range
AGE 0-3 DAYS: 96-292 NG/DL
4 DAYS-1 MONTH: 62-243 NG/DL
2-23 MONTHS: 81-281 NG/DL
2-6 YEARS: 83-252 NG/DL
7-11 YEARS: 92-219 NG/DL
12-19 YEARS: 83-215 NG/DL
>=20 YEARS: 80-200 NG/DL
| UNIT CODE | UNIT CODE NAME | ANALYTE | GENDER | AGE | REFERENCE RANGE | Units of Measure |
|---|---|---|---|---|---|---|
| 2818 | TOTAL T3 | T3T | NOT SPECIFIED | 0Y | 80-200 | NG/DL |
| 2818 | TOTAL T3 | T3T | NOT SPECIFIED | 3D | 96-292 | NG/DL |
| 2818 | TOTAL T3 | T3T | NOT SPECIFIED | 1M | 62-243 | NG/DL |
| 2818 | TOTAL T3 | T3T | NOT SPECIFIED | 23M | 81-281 | NG/DL |
| 2818 | TOTAL T3 | T3T | NOT SPECIFIED | 6Y | 83-252 | NG/DL |
| 2818 | TOTAL T3 | T3T | NOT SPECIFIED | 11Y | 92-219 | NG/DL |
| 2818 | TOTAL T3 | T3T | NOT SPECIFIED | 19Y | 83-215 | NG/DL |
| 2818 | TOTAL T3 | T3T | NOT SPECIFIED | 150Y | 80-200 | NG/DL |
| 2818 | TOTAL T3 | T3T | MALE | 0Y | 80-200 | NG/DL |
| 2818 | TOTAL T3 | T3T | MALE | 3D | 96-292 | NG/DL |
| 2818 | TOTAL T3 | T3T | MALE | 1M | 62-243 | NG/DL |
| 2818 | TOTAL T3 | T3T | MALE | 23M | 81-281 | NG/DL |
| 2818 | TOTAL T3 | T3T | MALE | 6Y | 83-252 | NG/DL |
| 2818 | TOTAL T3 | T3T | MALE | 11Y | 92-219 | NG/DL |
| 2818 | TOTAL T3 | T3T | MALE | 19Y | 83-215 | NG/DL |
| 2818 | TOTAL T3 | T3T | MALE | 150Y | 80-200 | NG/DL |
| 2818 | TOTAL T3 | T3T | FEMALE | 0Y | 80-200 | NG/DL |
| 2818 | TOTAL T3 | T3T | FEMALE | 3D | 96-292 | NG/DL |
| 2818 | TOTAL T3 | T3T | FEMALE | 1M | 62-243 | NG/DL |
| 2818 | TOTAL T3 | T3T | FEMALE | 23M | 81-281 | NG/DL |
| 2818 | TOTAL T3 | T3T | FEMALE | 6Y | 83-252 | NG/DL |
| 2818 | TOTAL T3 | T3T | FEMALE | 11Y | 92-219 | NG/DL |
| 2818 | TOTAL T3 | T3T | FEMALE | 19Y | 83-215 | NG/DL |
| 2818 | TOTAL T3 | T3T | FEMALE | 150Y | 80-200 | NG/DL |