Chronotherapeutic optimization of radioactive iodine therapy in differentiated thyroid cancer: The rationale for evening administration

Radioactive iodine (RAI) therapy remains a cornerstone in the management of differentiated thyroid cancer (DTC). The therapeutic efficacy of RAI depends on thyroid-stimulating hormone (TSH)-driven uptake <i>via</i> the sodium-iodide symporter (NIS). Although elevated TSH levels are routinely achieved before RAI administration, the circadian rhythm of TSH, which peaks overnight, is largely overlooked in treatment protocols. Aligning RAI administration with this physiological peak, particularly through evening dosing, may enhance iodine uptake, improve therapeutic efficacy, and reduce systemic exposure. Preclinical data and the known circadian regulation of TSH and NIS support this approach, although clinical validation is lacking. Evening dosing may also improve patient convenience and clinic workflow. However, logistical challenges and the absence of human trials present barriers to implementation. In this narrative review, we synthesize current evidence and tentatively propose the chronotherapeutic alignment of RAI timing as a novel, potentially impactful optimization strategy in DTC management. Prospective studies are needed to evaluate its clinical benefits and feasibility.