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Effect of timing of levothyroxine administration on the treatment of hypothyroidism: a three-period crossover randomized study

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Abstract

Aim

Hypothyroidism is a common clinical problem that is successfully treated with hormone substitutes in the form of levothyroxine (LT4). LT4 is a drug with a narrow therapeutic index and is usually administered by strict rules, standardly at least half an hour before breakfast. The aim of this study was to investigate a possible effect of different timings of administration on thyroid function status and lipid profile.

Methods

The study included patients with the diagnosis of primary hypothyroidism, which were using a stable dose of levothyroxine. They were randomized into three different groups regarding the timing of LT4 administration in a crossover fashion. Each timing regimen lasted for at least 8 weeks; timing regimen A—half an hour before breakfast; timing regimen B—an hour before the main meal of the day; timing regimen C—at bedtime (minimally 2 h after dinner). The hormones (TSH, fT3, fT4) and lipid profile (triglycerides, HDL-, LDL-, and total cholesterol) were measured before the study, at the beginning of every timing regimen and at the end of the study.

Results

Altogether, 84 patients finished the study. Different timings of LT4 administration were non-inferior in comparison to the standard one and between each other. Median differences in TSH level between baseline and timing regimens were: baseline vs. A = −0.017 95% C.I. (−0.400–0.192); baseline vs. B = −0.325 95% C.I. (−0.562–0.023); baseline vs. C = −0.260 95% C.I. (−0.475–0.000). There were no statistically significant differences in either TSH, fT4, or fT3 when compared between all three timing regimens of LT4 administration and the baseline. There were no statistically significant differences in any of the lipid profile parameters (triglycerides, HDL-, LDL-, and total cholesterol) when compared between all three timing regimens of LT4 administration and the baseline.

Conclusion

The three investigated timing regimens of LT4 administration were equally efficient and offer additional options regarding the treatment individualization.

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Abbreviations

BMI:

Body mass index

fT3:

Free triiodothyronin

fT4:

Free thyroxine

HDL:

High-density lipoprotein

IQR:

Interquartile range

LDL:

Low-density lipoprotein

LT4:

Levothyroxine

PPI:

Proton pump inhibitor

SmPC:

Summary of product characteristics

TSH:

Thyrotropin

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Funding

This study did not receive any external funding.

Authors’ contribution

All authors contributed to preparation of this manuscript.

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Correspondence to Marko Skelin.

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Conflict of interest

DR has served as principal investigator or co-investigator in clinical trials of AstraZeneca, Eli Lilly, MSD, Novo Nordisk, Sanofi Aventis, Solvay, and Trophos. He has received honoraria for speaking or advisory board engagements and consulting fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Lifescan–Johnson & Johnson, Novartis, Novo Nordisk, MSD, Merck Sharp & Dohme, Pfizer, Pliva, Roche, Salvus, Sanofi Aventis, and Takeda. MS has recevied honoraria for lectures from Roche. Other co-authors have no conflict of interest. TL has served as principal investigator or co-investigator in clinical trials of Bayer HealthCare AG, Sanofi Aventis, Institut de Recherches Internationales Servier, Zavante Therapeutics, and Novo Nordisk. He has received honoraria for speaking engagements from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, MSD.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Skelin, M., Lucijanić, T., Liberati-Čizmek, AM. et al. Effect of timing of levothyroxine administration on the treatment of hypothyroidism: a three-period crossover randomized study. Endocrine 62, 432–439 (2018). https://doi.org/10.1007/s12020-018-1686-1

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  • DOI: https://doi.org/10.1007/s12020-018-1686-1

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