Recombinant human thyrotropin (rhTSH)-aided radioiodine treatment for patients with nontoxic multinodular goiter may increase the risk of hypothyroidism but lead to a greater reduction in thyroid volume compared with radioiodine alone, according to a study in the Cochrane Database of Systematic Reviews.

Investigators sought to assess the effects of rhTSH-aided radioiodine treatment for nontoxic multinodular goiter. They searched CENTRAL, MEDLINE, and Scopus databases as well as the ICTRP Search Portal and through December 18, 2020, for relevant randomized controlled clinical trials (RCTs) with at least 12 months of follow-up.

The primary outcomes were health-related quality of life, hypothyroidism, and adverse events. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of the evidence.

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A total of 6 RCTs were included in the review. The studies had 321 participants—197 participants were randomized to rhTSH-aided radioiodine and 124 participants to radioiodine alone. All randomized participants completed the studies as planned, except in 1 study. The individual sample size ranged from 22 to 95, and follow-up ranged from 12 to 36 months.

Regarding health-related quality of life, no clear differences were found in symptom improvement in the 17 goiter-specific questions and overall quality of life question at 6 and 36 months (1 study, 85 participants; very low-certainty evidence). More than half of the participants reported no baseline symptoms for 9 of the goiter-specific items. A majority of patients reported improved symptoms after treatment for almost all goiter-specific items and in all treatment groups, when considering only participants who reported symptoms at baseline.

A total of 64 participants (32.5%) in the rhTSH-aided radioiodine group and 15 participants (12.1%) in the radioiodine-only group had hypothyroidism. Hypothyroidism increased after rhTSH-aided radioiodine treatment (risk ratio [RR] 2.53; 95% CI, 1.52 to 4.20; P < .001; 6 studies, 321 participants; moderate-certainty evidence).

Regarding adverse events, 118 participants (59.9%) in the rhTSH-aided radioiodine group and 60 participants (48.4%) in the radioiodine-only group had an event such as mild cervical discomfort or localized pain.

No evidence of a difference in adverse events was shown in the random-effects model (RR 1.24; 95% CI, 0.94 to 1.63; P = .13; 6 studies, 321 participants; low-certainty evidence). An RR of 1.23 (95% CI, 1.02 to 1.49; P = .03) in favor of radioiodine only was found in the fixed-effect model.

Thyroid volume was reduced more with rhTSH-aided radioiodine treatment compared with radioiodine only (mean difference, 11.91%; 95% CI, 4.43 to 19.40; P = .002; 6 studies, 268 participants; moderate-certainty evidence).

The researchers noted that the evidence was limited because only 6 RCTs with follow-up of at least 1 year or longer were available.

“Moderate-certainty evidence from 6 RCTs, in 321 participants, suggested that rhTSH radioiodine for nontoxic multinodular goiter reduces thyroid volume more than radioiodine alone,” the researchers concluded. “However, moderate-certainty evidence also showed radioiodine alone led to a lower risk of hypothyroidism.”


Huo Y, Xie J, Chen S, Wang H, Ma C. Recombinant human thyrotropin (rhTSH)-aided radioiodine treatment for non-toxic multinodular goitre. Cochrane Database Syst Rev. Published online December 28, 2021. doi: 10.1002/14651858.CD010622.pub2