Effect of recombinant human thyroid stimulating hormone on long-term salivary gland dysfunction in thyroid cancer patients treated with radioactive iodine. A systematic review

Adjuvant radioactive iodine (RAI) is administered to thyroid cancer patients following thyroidectomy for remnant tissue ablation and metastatic disease management. Patients are prepared with thyroid hormone withdrawal (THW) or recombinant human thyroid stimulating hormone (rhTSH). Long-term salivary gland dysfunction (LT-SGD) is a common, dosage-dependent, RAI adverse effect. Although rhTSH preparation seems to reduce LT-SGD, this effect could be due to lower RAI activity generally used in rhTSH-prepared patients. Therefore, this meta-analysis investigated the effect of preparation type on LT-SGD development. Literature search (PubMed, Medline, EmBase, Cochrane, Web of Science, LILACS, Google Scholar) was performed four times (January-November 2022) and studies reporting LT-SGD incidence ≥1 year after RAI in patients prepared with rhTSH/THW were identified. The LT-SGD risk ratio (RR) was estimated with various models considered for sensitivity analysis (fixed-effect, random-effects, study-quality adjusted, publication-bias adjusted, individual-patient-data meta-analysis adjusted for RAI). Subgroup analysis according to RAI activity (<3.7/≥3.7 GBq) also was performed. Literature search resulted in five studies (321 rhTSH, 632 THW patients). The pooled RRs according to various models were 0.65 (95% confidence interval -95CI, 0.49-0.86; fixed-effect); 0.62 (95CI, 0.38-1.02; random-effects); 0.72 (95CI, 0.54-0.96; quality adjusted); 0.76 (95CI, 0.58-0.99; publication-bias adjusted); 0.0.80 (95CI, 0.55-1.14; individual-patient-data meta-analysis). The pooled RRs stratified for RAI activity were 0.26 (95CI, 0.05-1.30) for <3.7 GBq; 0.75 (95CI, 0.57-0.98) for ≥3.7 GBq. The number of patients needed to be prepared with rhTSH to prevent one case of LT-SGD ranged between seven and thirty-seven. There is moderate-quality scientific evidence that rhTSH preparation may consistently protect salivary gland function.