Effectiveness of Different Thyroid Stimulating Hormone Thresholds for Thyroid Hormone Withdrawal - Aided Radioiodine Ablation in Patients With Differentiated Thyroid Cancer: A Systematic Review and Meta - Analysis

Background: Patients with differentiated thyroid cancer (DTC) may benefit of radioiodine ablation (RAI) to reduce the probability of thyroid cancer recurrence. Guidelines recommend that thyroid stimulating hormone (TSH) of >30mIU/L before RAI to optimize treatment response. However, evidence regarding this recommendation is conflicting. We conducted a systematic review and meta-analysis to compare outcomes (thyroid cancer recurrence and survival at 10 years of follow up) of stimulated TSH threshold before RAI with primary analysis focus on <30 mIU/L versus ≥30 mIU/L, and subgroup analysis on <90 mIU/L versus ≥90 mIU/L in patients with DTC after initial total thyroidectomy. Methods: The protocol for this study is registered and available online (CRD42020158354). Briefly, we searched several databases from their inception to April 2020. Reviewers, working independently and in duplicate selected studies for inclusion, extracted data, and evaluated each study’s risk of bias. We excluded studies that used recombinant human thyroid stimulating hormone before ablation. Results: We included five retrospective cohort studies, which enrolled a total of 2,514 patients. Risk of bias was low in four studies and high in one study. Mean age was 47 years old (ranged from 40.7 to 47.9) and most of them were female (69%). The most common DTC type was papillary thyroid cancer (78%). From those articles that reported tumor characteristics, 48% had a size ≤2cm (T1b) and 47% >2cm. Moreover, 73% of the patients had no regional lymph metastasis (N0). Two studies reported radioiodine mean dose given of 30 and 100 mci. A total of 301 patients were included in the TSH threshold <30 mIU/L group and 1788 patients in the TSH ≥30 mIU/L group. Comparing stimulated TSH threshold before RAI (<30 mIU/L versus ≥30 mIU/L), there was difference in recurrence at 1 year (RR 2.46 (C.I. 1.09-5.55) and at 20 years (RR 1.71 (C.I. 1.19 – 2.47). However, there was no difference in mortality at 20 years (RR 0.53 (Confidence Interval (C.I.) 0.12-2.23). In addition, 10-years recurrence was not different when we compared <90 mIU/L versus ≥90 mIU/L TSH (RR 1.06; 95%CI: 0.88 – 1.27). Conclusions: Mortality do not differ between recommended TSH goal (≥30 mIU/L) vs <30 mIU/L in thyroid hormone withdrawal-aided radioiodine ablation in DTC patients. However, the risk of recurrence is reduced when patients achieved a TSH level >30 UI/mL. These results suggest that patients may need to reach a stimulated TSH ≥30 mIU/L stimulated TSH threshold to be treated. Randomized trials are needed to confirm these findings.