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Comparative Study
. 2025 Nov;90(2):793-799.
doi: 10.1007/s12020-025-04375-9. Epub 2025 Aug 8.

Comparison of tablet versus liquid ethanol-free Levothyroxine in thyroidectomised patients

Laura Croce  1   2 , Spyridon Chytiris  2 , Marsida Teliti  1   2 , Jacopo Bertini  3 , Lidia Pizzuto  1 , Marzia Dal Molin  1 , Matteo Limiroli  1 , Benedetto Calì  4 , Flavia Magri  1   2 , Mario Rotondi  5   6
Affiliations
Comparative Study

Comparison of tablet versus liquid ethanol-free Levothyroxine in thyroidectomised patients

Laura Croce et al. Endocrine. 2025 Nov.

Abstract

Purpose: Since the introduction of an ethanol-free liquid levothyroxine formulation, only few studies assessed its therapeutic efficacy. The present study aimed to compare the efficacy of tablet (T-LT4) versus L-EF-LT4 in achieving the patient-specific TSH target in thyroidectomized patients. The primary objective was to assess whether the required LT4 dose differed between formulations in a real-life setting.

Methods: The study was conducted on 275 patients who underwent total thyroidectomy and were treated with either T-LT4 (n = 152) or L-EF-LT4 (n = 123) between 2020 and 2023. Clinical and biochemical data, including LT4 dose, BMI, TSH levels, and potential causes of malabsorption, were collected. The primary endpoint was the pro-kg LT4 dose required to achieve individualized TSH targets. Multivariate regression analysis was used to evaluate predictors of LT4 requirement.

Results: At final follow-up, 227 patients (82.5%) achieved their TSH target and were under stable doses of LT4 with no significant difference in mean LT4 dose between groups (T-LT4: 1.54 ± 0.35 µg/kg/day; L-EF-LT4: 1.60 ± 0.32 µg/kg/day, p = 0.160). TSH levels were comparable (p = 0.311). Regression analysis showed that age and BMI were inversely correlated with LT4 dose, while a diagnosis of differentiated thyroid cancer was positively correlated with LT4 dose. Formulation type was not a significant predictor.

Conclusion: In patients with post-surgical hypothyroidism, L-EF-LT4 demonstrated equivalent therapeutic efficacy to T-LT4 in terms of dose requirement and TSH control. These findings support the use of L-EF-LT4 as a viable alternative to tablet LT4, particularly in clinical scenarios where flexible timing of ingestion may improve patient compliance.

Keywords: Ethanol-free liquid Levothyroxine - levotirsol; Hypothyroidism; Levothyroxine; Thyroid; Total thyroidectomy.

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Conflict of interest statement

Compliance with ethical standards. Conflict of interest: The authors declare no competing interests. Informed consent: All patients signed an informed consent concerning the future use of their clinical-pathological data for research purposes. This study was formally approved by the Istituti Clinici Scientifici Maugeri IRCCS Ethical Committee (Protocol number CE 2418).

Figures

Fig. 1
Fig. 1
Sankey Diagram representing patient’s status at T1 and T2. * Patients lost at follow-up after T1
Fig. 2
Fig. 2
Comparison of mean daily per-kg dose between Tablet Levothyroxine (T-LT4) and Liquid Ethanol-Free Levothyroxine (L-EF-LT4) among patients reaching their TSH target at T2. Bars represent mean values and brackets represent standard Deviation
See this image and copyright information in PMC

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