Abstract: Following radioiodine therapy (RAI) of differentiated thyroid cancer, salivary and lacrimal glands may be injured, leading to dysfunctions. The incidence of these dysfunctions after RAI is poorly known, and no risk factors have been identified to date to define at-risk patients. The aims of this study are to characterize the dysfunction of salivary and lacrimal glands after RAI, and to identify risk factors of such dysfunctions. START (Salivary dysfuncTion After Radioiodine Treatment) is a prospective study launched in 2020, including 139 thyroid cancer patients, candidates for a RAI (45 and 94 patients received 1.1GBq and 3.7GBq 131I activity, respectively) in Pitié-Salpêtrière hospital, Paris, France. Follow-up was based on 3 scheduled visits: immediately before RAI (T0), 6 months (T6) and 18 months (T18) later. At each visit, questionnaires on salivary disorders (validated French tool), dry eye (OSDI© Questionnaire), and anxiety/depression symptoms (HAD scale) were administered. At T0 and T6, individual salivary flow measurements (with and without salivary gland stimulation) were performed. The doses to the salivary glands were evaluated through a dosimetric reconstruction based on recordings from thermoluminescent dosimeters directly positioned on the patients. In the present work, data for the T0 and T6 visits were analysed based on descriptive analyses and random-effects logistic and linear regressions. Complete information was provided for 136 patients (71% women, mean age=47.1 (±14.1) y). Mean doses to the salivary glands were 0.7 (±0.2) and 2.3 (±0.9) Gy for the 1.1GBq and 3.7GBq 131I-activity groups, respectively. At T6, 18% and 22% of the study population without any symptoms at T0 reported dry eye and/or dry mouth feeling, respectively. Stimulated saliva flow rate significantly decreased from T0 to T6 (2.14 (±0.86) and 1.93 (±0.78) mL/min, p<10-3, respectively). Univariate analyses allowed to highlight age, menopause, depression and anxiety symptoms, history of systemic disease, and not taking painkillers in the last 3 months as risk factors or variables significantly associated with salivary or lachrymal disorders. Multivariate analyses adjusted on the previous variables showed significant dose-responses relationships between doses to the salivary glands and dry mouth sensation or stimulated saliva flow rate, as well as between administered activity and dry mouth sensation or lachrymal disorders. This work presents the 6 months follow-up results of the START study, showing higher salivary and lacrimal gland disorders after RAI. Further analyses will include saliva biochemical concentrations, genetic and epigenetic variants as risk factors, and quality of life of patients at T6 and T18.