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The Levothyroxine Odyssey: Navigating the Path of Survivorship in Thyroid Cancer

Article information

Endocrinol Metab. 2024;39(2):283-284
Publication date (electronic) : 2024 April 25
doi : https://doi.org/10.3803/EnM.2024.201
Department of Endocrinology and Metabolism, Chosun University Hospital, Gwangju, Korea
Corresponding author: Jin Hwa Kim. Department of Endocrinology and Metabolism, Chosun University Hospital, 365 Pilmun-daero, Dong-gu, Gwangju 61453, Korea Tel: +82-62-220-3011, Fax: +82-62-223-3316, E-mail: endocrine@chosun.ac.kr
Received 2024 March 29; Accepted 2024 April 4.

The management of thyroid cancer presents a multifaceted challenge, necessitating a comprehensive approach that includes surgery, radioactive iodine therapy, and thyroid-stimulating hormone (TSH) suppression through levothyroxine [1]. These interventions aim to improve patient outcomes, but concerns persist regarding their long-term effects [2-4]. The increasing number of thyroid cancer survivors underscores the importance of meticulous long-term management strategies [5]. Crucial to this approach is postoperative TSH suppression therapy with levothyroxine, which plays a pivotal role in reducing the risk of disease recurrence [6]. However, there exists a notable gap in current research regarding the potential implications and risks associated with prolonged levothyroxine use.

In the latest issue of Endocrinology and Metabolism, the study by Kim et al. [7] sheds light on the relationship between levothyroxine dosage and subsequent primary cancers (SPCs) among thyroid cancer survivors. Drawing from the Korean National Health Insurance database, the study examined a cohort of 342,920 individuals diagnosed with thyroid cancer between 2004 and 2018. The findings provide valuable insights into the potential association between levothyroxine dosage and SPC risk, prompting a reevaluation of dosing strategies in thyroid cancer survivors.

The study’s rigorous methodology, including stringent cohort selection, dosage stratification, and adjustment for confounding variables, forms a robust foundation for its conclusions. Particularly notable is the observed association between high-dose levothyroxine and increased SPC risk, particularly in the gastrointestinal and hepato-biliary-pancreatic systems. These findings underscore the importance of tailored TSH suppression therapy, balancing the benefits against the potential risks of SPC development. However, it is also necessary to acknowledge the study’s limitations, such as reliance on health insurance claims data and the inability to assess individual patient compliance. Despite these challenges, the rigorous approach to data analysis and the sensitivity analyses conducted by Kim et al. [7] strengthen the study’s validity and reliability.

The mechanistic basis underlying the observed association between levothyroxine dosage and SPC risk is multifaceted. Proposed mechanisms include the mitogenic effects of TSH suppression on thyroid tissue remnants, alterations in cellular proliferation pathways, and the modulation of oncogenic signaling cascades [8-10]. However, comprehensive research will be necessary to elucidate the precise interplay between thyroid hormones, TSH suppression, and carcinogenesis.

The findings of recent population-based studies have significant implications for clinical practice. Individualized treatment approaches that incorporate patient-specific factors, tumor characteristics, and treatment goals are crucial for optimizing therapeutic outcomes and minimizing long-term sequelae. Future research should focus on elucidating the mechanisms underlying the observed association between levothyroxine dosage and SPC risk. Prospective studies leveraging advanced molecular and genetic profiling techniques are warranted to unravel the complex interplay between thyroid hormone signaling pathways and oncogenic processes. Moreover, alternative TSH suppression strategies, such as dose titration and tailored treatment algorithms, hold promise for optimizing therapeutic efficacy while mitigating SPC risk.

As we navigate the evolving landscape of thyroid cancer treatment, it is essential to remain vigilant regarding emerging evidence and its implications for patient care. The association between levothyroxine dosage and the risk of SPCs is a critical area of study, necessitating collaboration across different fields to improve our understanding and guide treatment decisions. Through diligent research, compassionate patient care, and ongoing collaboration, we can leverage knowledge to improve thyroid cancer treatment. Together, we can strive for a future where every patient receives personalized, evidence-based care that emphasizes safety, effectiveness, and patient well-being [11,12].

In conclusion, this pivotal study underscores the significance of a nuanced approach to levothyroxine therapy in thyroid cancer survivors. By carefully weighing benefits and risks, clinicians can optimize outcomes and improve patients’ quality of life. Continued research is needed to clarify the mechanisms underlying the observed associations and further refine therapeutic strategies, ultimately advancing survivorship care.



No potential conflict of interest relevant to this article was reported.


1. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016;26:1–133.
2. Yu J, Kaur R, Ayeni FE, Eslick GD, Edirimanne S. Cardiovascular outcomes of differentiated thyroid cancer patients on long term TSH suppression: a systematic review and meta-analysis. Horm Metab Res 2023;55:379–87.
3. Zhang H, Yang Y, Gao C, Tian L. Effect of thyroid-stimulating hormone suppression therapy on cardiac structure and function in patients with differentiated thyroid cancer after thyroidectomy: a systematic review and meta-analysis. Endocr Pract 2024;30:177–86.
4. Ku EJ, Yoo WS, Lee EK, Ahn HY, Woo SH, Hong JH, et al. Effect of TSH suppression therapy on bone mineral density in differentiated thyroid cancer: a systematic review and meta-analysis. J Clin Endocrinol Metab 2021;106:3655–67.
5. Boucai L, Zafereo M, Cabanillas ME. Thyroid cancer: a review. JAMA 2024;331:425–35.
6. Chen DW, Lang BH, McLeod DS, Newbold K, Haymart MR. Thyroid cancer. Lancet 2023;401:1531–44.
7. Kim MS, Lee JW, Hyun MK, Song YS. Risk of subsequent primary cancers in thyroid cancer survivors according to the dose of levothyroxine: a nationwide cohort study. Endocrinol Metab (Seoul) 2024;39:288–99.
8. Goemann IM, Romitti M, Meyer EL, Wajner SM, Maia AL. Role of thyroid hormones in the neoplastic process: an overview. Endocr Relat Cancer 2017;24:R367–85.
9. Yen PM. Physiological and molecular basis of thyroid hormone action. Physiol Rev 2001;81:1097–142.
10. Kress E, Samarut J, Plateroti M. Thyroid hormones and the control of cell proliferation or cell differentiation: paradox or duality? Mol Cell Endocrinol 2009;313:36–49.
11. Obeid LA, Dhillon HM, Tan SY, Vardy JL. Is there a need for change in cancer survivorship care?: a qualitative exploration of survivor experiences and needs at the Sydney Cancer Survivorship Centre Clinic. Support Care Cancer 2023;31:642.
12. Goldfarb M, Franco AT. Survivorship, quality of life, and transition to adult care for pediatric and adolescent thyroid cancer survivors. Thyroid 2022;32:1471–6.

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