Early versus delayed oral sialagogues for the prevention of salivary gland dysfunction after radioiodine therapy in differentiated thyroid cancer: a systematic review.

Salivary gland dysfunction is a recognized complication of radioactive iodine (RAI) therapy for differentiated thyroid cancer. Oral sialagogues are commonly recommended, but their optimal timing remains uncertain. This systematic review compares early (<24 h) versus delayed (>24 h) sialagogue initiation. A literature search was conducted in Embase, PubMed, CINAHL, and Cochrane from inception to January 2026. "Early" protocols initiated stimulation within 24 h post-RAI, while "delayed" protocols initiated after 24 h. Methodological quality and risk of bias were assessed using Cochrane's ROBINS-I (Risk Of Bias In Non-randomized Studies of Interventions, 2016) tool. Three observational studies were included, comprising 818 adults with reported mean ages of 43-59 years. Interventions consisted primarily of lemon candy or oral vitamin C tablets. Primary outcomes included acute sialadenitis (pain and/or swelling), taste dysfunction, and xerostomia. Findings regarding acute salivary gland outcomes were inconsistent. Two earlier studies reported higher rates of acute sialadenitis with early stimulation (54.7-63.8% vs. 34.4-36.8%), taste dysfunction (37.5-39.0% vs. 18.8-25.6%), and xerostomia (23.8-46.9% vs. 11.2-29.7%) compared with delayed initiation. In contrast, the most recent propensity score-matched study, which evaluated a composite endpoint of acute salivary gland damage, reported lower event rates with early stimulation (4.78% vs. 15.22%). This review underscores how evidence regarding the optimal timing of sialagogue initiation after RAI remains inconsistent. These heterogeneous findings highlight the need for high-quality randomized controlled trials to establish evidence-based recommendations for sialagogue timing after RAI therapy.