TSH Cutoffs and Recurrence Risk in Differentiated Thyroid Carcinomas: A Systematic Review and Meta-Analysis

Abstract Context The current American Thyroid Association (ATA) guidelines recommend tailored TSH suppression, considering the recurrence risk of differentiated thyroid cancer (DTC); however, the evidence is limited. Objective This meta-analysis aimed to investigate the risk of recurrence in patients with DTC, stratified by the ATA risk of recurrence, according to variable thyrotropin (TSH) cutoffs (0.1, 0.5, and 2.0 mIU/L). Methods We searched Ovid-Medline, EMBASE, and Cochrane databases for studies reporting the recurrence rate of DTCs based on TSH cutoffs through March 2024. The search terms used included “thyroid neoplasm” OR “cancer,” “TSH” OR “thyroid stimulating hormone,” “suppress” OR “supplementation,” and “thyroidectomy”. Results Two randomized controlled trials and 7 observational studies, including 5320 patients, were analyzed, with an overall recurrence rate of 18%. The pooled recurrence risk for DTCs at each TSH cutoff (0.1, 0.5, and 2.0 mIU/L) was not significant. In the subgroup analysis, the pooled hazard ratios (HRs) stratified by the ATA risk of recurrence (low- and high-risk DTCs) did not differ according to TSH levels. However, the risks of recurrence increased at serum TSH of 0.1 mIU/L or greater (HR 2.27; 95% CI, 1.29-3.99) and TSH of 2.0 mIU/L or greater (HR 1.36; 95% CI, 1.001-1.84) in a leave-one-out meta-analysis after removing the study that significantly influenced the analysis. Patients with distant metastases had a higher risk of recurrence (HR 3.3; 95% CI, 1.53-7.10) when maintaining a TSH greater than or equal to 0.1 mIU/L. Conclusion The degree of TSH suppression did not affect the overall risk of DTC recurrence. However, TSH suppression may be beneficial in reducing the recurrence risk in high-risk patients with distant metastases.