When to order Triiodothyronine (T3) for patients with hypothyroidism?

When to Order T3 Testing in Hypothyroidism

T3 testing is generally not indicated for routine management of hypothyroidism in patients on levothyroxine therapy, as TSH and free T4 are sufficient for monitoring treatment adequacy. 1, 2

Primary Screening and Monitoring: TSH and Free T4 Are Sufficient

• TSH is the most sensitive test for monitoring thyroid function with sensitivity above 98% and specificity greater than 92%, making it the primary screening tool for hypothyroidism 1
• For initial evaluation of suspected thyroid dysfunction, measure TSH as the first-line test, and if TSH is abnormal, measure free T4 to distinguish between subclinical hypothyroidism (normal free T4) and overt hypothyroidism (low free T4) 1
• Both TSH and free T4 levels should be measured to assess thyroid hormone replacement adequacy and avoid complications, distinguishing between adequate replacement, undertreatment, and overtreatment 1

When T3 Testing Is NOT Useful

• In levothyroxine-induced over-replacement, T3 levels bear little relation to thyroid status and normal T3 levels can be seen in over-replaced patients, making T3 measurement of doubtful clinical value in this situation 2
• T3 is a sensitive marker of endogenous hyperthyroidism, but in levothyroxine (T4)-induced hyperthyroidism, there is no reason for T3 to be elevated 2
• In patients with over-replacement (fully suppressed TSH <0.02 mU/L and high free T4 >27 pmol/L), none had a raised T3, demonstrating that T3 measurement does not add information for detecting over-replacement 2
• The most discriminant T3 level for detecting over-replacement was 1.6 nmol/L with only 58% sensitivity and 71% specificity, which is inadequate for clinical decision-making 2

Limited Scenarios Where T3 May Be Considered

Suspected T3 Toxicosis

• Calculation of the free T3 index might make possible the diagnosis of T3-toxicosis in a patient with a normal free T4 index and normal total T3 3
• Hyperthyroid patients with apparent T4-toxicosis and normal total T3 may have an elevated free T3 index and thus physiologically elevated levels of both thyroid hormones 3

Immune Checkpoint Inhibitor-Induced Thyroiditis

• In the hyperthyroid phase of thyroiditis, patients may benefit from beta blockers if symptomatic, and thyroid hormones should be introduced if the patient becomes hypothyroid (low free T4/T3, even if TSH is not elevated) 4
• Monitor closely with regular symptom evaluation and free T4 testing every 2 weeks during the hyperthyroid phase 4

Persistent Symptoms Despite Normal TSH/T4

• If TSH remains normal and symptoms persist in patients with subclinical hypothyroidism, consider checking T3 levels if not already done, as this can help identify subtle thyroid dysfunction 5
• However, this remains controversial as approximately 15% of patients on L-T4 replacement therapy with normalized TSH report continued fatigue and other hypothyroid symptoms, but the role of T3 testing in these patients is not well-established 6

Common Pitfalls to Avoid

• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, but T3 measurement will not help identify this over-replacement—TSH and free T4 are sufficient 1
• Avoid ordering T3 routinely in patients on levothyroxine replacement, as it does not add clinically useful information for dose adjustment 2
• Do not use T3 levels to exclude over-replacement, as normal T3 results can be falsely reassuring in patients who are actually over-replaced based on TSH and free T4 2

Research Context on T3 Levels and Thyroid Replacement

• Patients on all types of L-T4 treatment had higher reverse T3 (rT3) levels than those not on L-T4 treatment, with the highest rate of elevated rT3 (20.9%) in patients taking T4 alone 6
• The lowest levels of rT3 were found in patients on preparations containing L-T3 alone, though the clinical significance of this finding remains uncertain 6
• Thyroid hormone replacement with LT4 alone does not restore physiological tissue levels of thyroid hormones, particularly T3, but randomized controlled trials have failed to demonstrate superiority for combination LT4 + T3 therapy 7