Meristoudis G, Savvidis C, Ilias I. Chronotherapeutic optimization of radioactive iodine therapy in differentiated thyroid cancer: The rationale for evening administration. World J Exp Med 2025; 15(4): 110893 [DOI: 10.5493/wjem.v15.i4.110893]
Corresponding Author of This Article
Ioannis Ilias, MD, PhD, Director, Department of Endocrinology, Hippocration General Hospital, No. 63 Evrou Street, Athens GR-11527, Greece. iiliasmd@yahoo.com
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Endocrinology & Metabolism
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Minireviews
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Dec 20, 2025 (publication date) through Dec 19, 2025
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World Journal of Experimental Medicine
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2220-315x
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Meristoudis G, Savvidis C, Ilias I. Chronotherapeutic optimization of radioactive iodine therapy in differentiated thyroid cancer: The rationale for evening administration. World J Exp Med 2025; 15(4): 110893 [DOI: 10.5493/wjem.v15.i4.110893]
World J Exp Med. Dec 20, 2025; 15(4): 110893 Published online Dec 20, 2025. doi: 10.5493/wjem.v15.i4.110893
Chronotherapeutic optimization of radioactive iodine therapy in differentiated thyroid cancer: The rationale for evening administration
Georgios Meristoudis, Christos Savvidis, Ioannis Ilias
Georgios Meristoudis, Department of Nuclear Medicine, Hippokration General Hospital, Thessaloniki 54643, Greece
Christos Savvidis, Ioannis Ilias, Department of Endocrinology, Hippocration General Hospital, Athens GR 11527, Greece
Author contributions: Meristoudis G, Savvidis C, Ilias I conceived this paper, searched the literature and drafted the manuscript, wrote the final version to be submitted.
Conflict-of-interest statement: All the authors declare that they have no conflict of interest regarding this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ioannis Ilias, MD, PhD, Director, Department of Endocrinology, Hippocration General Hospital, No. 63 Evrou Street, Athens GR-11527, Greece. iiliasmd@yahoo.com
Received: June 18, 2025 Revised: June 26, 2025 Accepted: September 19, 2025 Published online: December 20, 2025 Processing time: 184 Days and 19.5 Hours
Abstract
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 via 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.
Core Tip: Radioactive iodine (RAI) therapy is central to differentiated thyroid cancer management, relying on thyroid-stimulating hormone (TSH)-driven sodium-iodide symporter activity. Current protocols elevate TSH but overlook its circadian peak overnight. Aligning RAI administration with this peak via evening dosing may enhance iodine uptake, improve efficacy, reduce exposure, and optimize workflow. Preclinical evidence supports this chronotherapeutic approach, although clinical data are lacking. This review synthesizes existing evidence and proposes timed RAI administration as a novel strategy warranting prospective evaluation.
