Tailoring TSH suppression in differentiated thyroid carcinoma: evidence, controversies, and future directions.

Purpose: This review focus on the controversial benefits of thyroid hormone suppression therapy (THST) in differentiated thyroid carcinoma (DTC) and its associated risks, highlighting the need for individualized strategies to optimize therapeutic outcomes and guide future research.

Methods: A systematic literature search on TSH suppression in DTC over the past 10 years was conducted, prioritizing RCTs, large cohort studies, and non-inferiority trials, with additional references identified from retrieved articles.

Results: Tailored postoperative TSH strategies should consider factors such as risk stratification, treatment modality, histologic subtype, and adverse effect risks. In this context, mechanistic studies offer potential insights that could inform personalized TSH management, though further validation is required. Clinical evidence on THST in DTC remains controversial, particularly for high-risk patients, where support for stringent TSH suppression (<0.1 mU/L) is limited. Data for intermediate-risk DTC are insufficient due to cohort heterogeneity, while TSH suppression in low-risk DTC is largely discouraged. The well-documented adverse effects of excessive THST, including cardiovascular complications and osteoporosis, further provide a strong rationale against its routine use. Additionally, achieving and maintaining target TSH levels in real-world practice remains challenging, underscoring the need for refined approaches.

Conclusion: Current evidence provides limited support for the TSH targets recommended by the 2015 ATA guidelines. Optimizing postoperative TSH management should account for individualized factors, including risk stratification, treatment modalities, histologic subtypes, and susceptibility to adverse effects. Future research should prioritize well-designed studies with clearly defined suppression levels and appropriate confounder adjustments, emphasizing personalized approaches to balance therapeutic benefits and adverse effects.