T3 (Triiodothyronine): Definition and Clinical Testing Indications
T3 is one of the two main thyroid hormones (along with T4/thyroxine) and should be checked selectively—primarily when TSH is suppressed but free T4 is normal (to diagnose hyperthyroidism), or in specific scenarios like suspected T3-toxicosis or monitoring central hypothyroidism. 1
What is T3?
T3 (triiodothyronine) is the biologically active thyroid hormone that binds to thyroid hormone receptors throughout the body. 2 It is produced both directly by the thyroid gland and through peripheral conversion of T4 to T3 by deiodinase enzymes. 3 While T3 is the more potent hormone, it circulates at much lower concentrations than T4.
When to Check T3: Algorithmic Approach
Primary Scenario: Suspected Hyperthyroidism with Discordant Results
- Check T3 when TSH is suppressed (<0.1-0.4 mIU/L) but free T4 is normal, as this pattern may indicate T3-toxicosis or early hyperthyroidism. 2, 1
- This is particularly relevant in thyroiditis associated with immune checkpoint inhibitors, where thyrotoxicosis presents with high free T4 or T3 levels with low/normal TSH. 2
Secondary Scenario: Confirming Overt Hyperthyroidism
- Measure T3 alongside free T4 when TSH is low or undetectable to confirm overt hyperthyroidism, which is biochemically defined by low TSH and elevated T4 or T3. 2
- Overt hyperthyroidism can present with either elevated T4 or T3, making T3 measurement diagnostically important in this context. 2
Tertiary Scenario: Central Hypothyroidism Monitoring
- In central (secondary/tertiary) hypothyroidism, measure free T4 and T3 concentrations directly since TSH levels are diagnostically misleading in pituitary or hypothalamic dysfunction. 1, 4
- TSH cannot be used to monitor adequacy of replacement in central hypothyroidism. 4
When NOT to Check T3: Critical Caveats
Do Not Use T3 to Assess Levothyroxine Over-Replacement
- T3 measurement adds no diagnostic value in patients on levothyroxine replacement therapy, even when over-replacement is suspected. 5
- In a study of 542 patients on levothyroxine, none of the 33 over-replaced patients (defined by suppressed TSH <0.02 mU/L and high free T4 >27 pmol/L) had elevated T3 levels. 5
- The sensitivity and specificity of T3 for detecting over-replacement were only 58% and 71% respectively, making it clinically unreliable. 5
- Normal T3 levels can falsely reassure clinicians and mask true over-replacement, potentially allowing harmful over-treatment to continue. 5
Do Not Use T3 for Initial Thyroid Screening
- TSH is the first-line test for investigating thyroid function, with 98% sensitivity and 92% specificity. 1
- The American Academy of Family Physicians and American College of Physicians recommend measuring free T4 only after TSH is abnormal, with T3 reserved for the specific scenarios outlined above. 1
Do Not Use T3 for Routine Monitoring of Primary Hypothyroidism
- TSH is the most important parameter to monitor adequacy of levothyroxine replacement in primary hypothyroidism. 4
- T3 levels bear little relation to thyroid status in patients on levothyroxine replacement. 5
Important Clinical Pitfalls
Reverse T3 (rT3) testing has no established clinical utility despite its popularity in functional medicine circles. 6 While rT3 is elevated in severe illness ("euthyroid sick syndrome") and correlates with T4 levels in patients on levothyroxine, there is insufficient evidence to support using rT3 measurements to guide treatment decisions. 6
Always confirm abnormal thyroid function tests with repeat testing before initiating treatment, as non-thyroidal illness can interfere with results. 1 TSH secretion is sensitive to conditions other than thyroid dysfunction, and many professional groups recommend repeating tests over 3-6 month intervals in asymptomatic persons unless TSH is >10.0 or <0.1 mIU/L. 2
In hypophysitis (particularly from immune checkpoint inhibitors), start steroids before thyroid hormone replacement when both adrenal insufficiency and hypothyroidism are present, to avoid precipitating an adrenal crisis. 2