When to Test for T3
T3 testing should be reserved for specific clinical scenarios and is NOT routinely indicated for monitoring hypothyroid patients on levothyroxine therapy. 1, 2
Primary Indication: Suspected Hyperthyroidism with Discordant Results
Order T3 when TSH is suppressed (<0.1-0.4 mIU/L) but free T4 remains normal, as this pattern suggests T3-toxicosis or early hyperthyroidism. 3, 1, 4 This is the most important clinical scenario where T3 provides diagnostic value.
- In highly symptomatic patients with minimal free T4 elevations, T3 can help confirm hyperthyroidism, particularly in thyroiditis associated with immune checkpoint inhibitors. 3
- When TSH is low or undetectable, measure T3 alongside free T4 to confirm overt hyperthyroidism (biochemically defined by low TSH and elevated T4 or T3). 1
- T3 is particularly valuable for detecting T3-toxicosis, where patients are hyperthyroid but T4 levels are deceptively normal. 4
Secondary Indication: Central Hypothyroidism
In suspected central (secondary/tertiary) hypothyroidism from pituitary or hypothalamic dysfunction, measure free T4 and T3 directly, since TSH levels are diagnostically misleading in these conditions. 1, 5
- This includes cases of hypophysitis, particularly from immune checkpoint inhibitors, where both adrenal insufficiency and hypothyroidism may coexist. 1
- In these patients, start steroids before thyroid hormone replacement to avoid precipitating an adrenal crisis. 1
When NOT to Test T3
Do NOT order T3 for monitoring levothyroxine dosing in hypothyroid patients. 2, 4 This is explicitly discouraged by the Endocrine Society's Choosing Wisely campaign and represents inappropriate testing. 2
- In levothyroxine-induced over-replacement, T3 levels remain normal even when patients are biochemically over-replaced (suppressed TSH, elevated free T4). 6
- T3 has poor discriminant power (sensitivity 58%, specificity 71%) for detecting levothyroxine over-replacement and provides no additional clinical value beyond TSH and free T4. 6
- Most circulating T3 (80%) comes from peripheral conversion of T4, not thyroid secretion, making it an unreliable marker of thyroid hormone production in patients on levothyroxine. 5
Specialized Scenarios (Less Common)
T3 may have limited utility in:
- Monitoring thyroid hormone replacement therapy in select cases (though not routine monitoring). 4
- Evaluating amiodarone-induced thyrotoxicosis. 4
- Predicting outcomes of antithyroid drug therapy in Graves' disease. 4
Critical Caveats
- Always confirm abnormal thyroid function tests with repeat testing before initiating treatment, as non-thyroidal illness can interfere with results. 1
- TSH and free T4 should be the initial tests for investigating thyroid function; T3 is reserved for specific clinical scenarios where hyperthyroidism is suspected despite normal TSH and free T4. 1
- Immunoassays for T3 can be affected by alterations in serum binding proteins that occur in many physiological and disease states, potentially giving falsely normal values. 7