Improved adequacy of levothyroxine treatment in low-risk differentiated thyroid cancer using the 2025 ATA criteria: a multicenter real-world analysis of 1,016 patients.

BACKGROUND

Levothyroxine titration is essential in low-risk differentiated thyroid cancer (DTC).

OBJECTIVE

To compare levothyroxine treatment adequacy, response distribution, and determinants of inadequacy in a large real-world cohort applying the 2015 versus 2025 American Thyroid Association (ATA) criteria.

METHODS

We conducted a multicenter, retrospective cohort study including 1,016 adults with low-risk DTC (median follow-up: 79 months). Dynamic risk stratification and levothyroxine treatment adequacy - defined according to framework-specific thyrotropin (TSH) targets - were assessed at 12 months and at the last visit. Secondary outcomes included rates of overtreatment and undertreatment. Multivariable logistic regression identified factors associated with adequacy among excellent or indeterminate responders.

RESULTS

Under the ATA-2025 criteria, the proportion of patients with an excellent response increased to 72.0% at 12 months and 86.9% at last visit, compared with 62.3 and 77.8% using the ATA-2015 criteria. Treatment adequacy changed from 26.0% at 12 months and 39.6% at the last follow-up visit with ATA-2015 to 40.7 and 67.4% with ATA-2025 (both P < 0.001). Under ATA-2015, inadequacy was driven by overtreatment among excellent responders (61.8% at 12 months; 30.5% at final evaluation) and undertreatment among indeterminate responders (48.4%; 62.2%). Applying the ATA-2025 criteria reclassified overtreated excellent responders as 51.9 and 25.5% and undertreated indeterminate responders as 6.6 and 8.8%, respectively. At the last visit, older age modestly favored adequacy (OR: 1.02 per year, 1.00-1.03) and levothyroxine dose instability strongly predicted inadequacy (OR: 0.12 for adequacy, 0.08-0.16).

CONCLUSION

Applying the ATA-2025 criteria increases the proportion of patients classified as having adequate TSH control and decreases the proportion labeled as over- or undertreated under the 2015 framework, reflecting the broader, risk-adapted TSH targets introduced in 2025.