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Levothyroxine Dosing for Thyroid-Stimulating Hormone Suppression in Patients with Differentiated Thyroid Cancer after Total Thyroidectomy

Article information

Endocrinol Metab. 2024;39(4):576-578
Publication date (electronic) : 2024 August 26
doi : https://doi.org/10.3803/EnM.2024.401
Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
Corresponding author: Mijin Kim Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 49241, Korea Tel: +82-51-240-7738, Fax: +82-51-254-3237, E-mail: mijinkim08@gmail.com
Received 2024 July 30; Accepted 2024 August 10.

The suppression of thyroid-stimulating hormone (TSH) using levothyroxine (LT4) is crucial in managing differentiated thyroid cancer (DTC) after total thyroidectomy (TT) [1]. DTC cells express the TSH receptors on their cell membranes and respond to TSH by increasing the expression of several thyroid-specific proteins and accelerating the cell growth rate [2]. To reduce the risk of recurrence, TSH suppression using supraphysiological doses of LT4 is commonly employed [2-4]. International guidelines stratify the recurrence risk of DTC and recommend a TSH suppression level of 0.1 to 0.5 mIU/L for intermediate-risk DTC (weak recommendation, low-quality evidence) and <0.1 mIU/L for high-risk DTC (strong recommendation, moderate-quality evidence) [1]. Although TSH suppression therapy reduces the recurrence rate and cancer-related mortality, the optimal degree of suppression required to achieve these goals remains unclear [5].

Inadequate dosing may result in hypothyroidism or thyrotoxicosis, each of which is associated with various symptoms and complications. Overtreatment that causes thyrotoxicosis is linked to weight loss, insomnia, heat intolerance, and cardiovascular or skeletal issues, including arrhythmias and osteoporosis [6-8]. Conversely, insufficient treatment may lead to adverse changes in several metabolic parameters and a high-risk of recurrence [9]. Additionally, TSH suppression therapy affects the quality of life (QoL) of patients with DTC [7,10]. A recent Korean multicenter prospective study examined the effect of TSH suppression postthyroidectomy on health-related QoL in patients with DTC [11]. In the short-term postoperative period, patients who did not receive TSH suppression therapy reported better physical healthrelated QoL scores. Therefore, achieving the optimal LT4 dose to maintain TSH suppression is crucial for preventing tumor recurrence while minimizing adverse effects.

In a recent article in Endocrinology and Metabolism, Ryu et al. [12] presented valuable insights into the optimal dose of LT4 required to achieve mild TSH suppression in patients who have undergone TT for DTC. The authors reviewed the electronic medical records of 351 patients with DTC who underwent TT. After excluding patients with missing body mass index (BMI) data, TSH levels below 0.1 mIU/L, or above 0.5 mIU/L, 123 patients were included. This rigorous selection process ensured a well-defined and relevant study population. The mean LT4 dose relative to actual body weight was 1.8 μg/kg/day. A higher BMI was associated with higher absolute LT4 requirements but lower weight-based LT4 doses, particularly in younger patients aged 20 to 39 years. This finding underscores the importance of considering age and BMI when determining the LT4 dosage to achieve optimal TSH suppression.

This study suggests that LT4 dosing should be personalized based on BMI and age to achieve optimal TSH suppression after TT in patients with DTC [12]. A recent review examined various LT4 dosing protocols after thyroidectomy and highlighted the complexity and variability in determining the optimal dose [9]. Traditional dosing often starts at approximately 1.6 μg/kg of body weight, with adjustments based on thyroid function tests and patient symptoms [13]. However, empirical dosing, which is based on patients with primary hypothyroidism, frequently requires adjustments. This indicates that factors other than body weight, such as BMI, age, body surface area, iron supplementation, mineral supplementation, and sex, play crucial roles in patients’ response to LT4 [9]. The findings of Ryu et al. [12] align with this perspective, emphasizing BMI as a critical factor in determining LT4 dose. They demonstrated that a higher BMI was correlated with a lower weight-based LT4 dose, a nuance that has not been fully captured in earlier empirical dosing protocols. Additionally, the authors found an inverse relationship between age and weight-based LT4 doses for mild TSH suppression. This trend was especially pronounced in female patients, suggesting that younger adults with lower BMI require higher LT4 doses to achieve the same level of TSH suppression as older individuals. This is consistent with the general understanding that younger individuals have higher metabolic rates and greater lean body mass, necessitating higher LT4 doses [14,15]. These findings support the need for more individualized dosing strategies that consider BMI and age.

Although this study provides valuable insights, it highlights several areas for future research. The study population was predominantly Korean and female, which may limit the generalizability of the findings. Future research should aim to validate these findings in larger and more diverse populations and explore additional factors that may influence LT4 dosing, such as lean body mass and body surface area. Additionally, prospective studies are needed to clarify the usefulness of personalized LT4 dosing, considering BMI, age, sex, and body weight to rapidly reach the target TSH level after TT.

In conclusion, the findings of this study have significant implications for clinical practice. Based on a more accurate understanding of the relationships among BMI, age, and LT4 dosage, healthcare providers can tailor LT4 therapy more precisely, ensuring effective TSH suppression while minimizing the risk of adverse effects. This personalized approach to LT4 dosing may lead to better patient outcomes and more efficient management of DTC. Additional prospective studies of LT4 therapy immediately after thyroidectomy in diverse populations are required to validate these findings.

Notes

CONFLICTS OF INTEREST

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

Acknowledgements

This work was supported by clinical research grant from Pusan National University Hospital in 2023.

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