L-Thyroxine intake as a potential risk factor for the development of fatigue in breast cancer patients undergoing chemotherapy

  • Martina E. Schmidt
  • Joachim Wiskemann
  • Theron Johnson
  • Nina Habermann
  • Andreas Schneeweiss
  • Karen Steindorf
Original Article

Abstract

Purpose

L-Thyroxine is one of the most commonly prescribed drugs and accordingly used by many breast cancer patients with thyroid disorders. Hence, potential interactions of chemotherapy with L-thyroxine, possibly contributing to fatigue, would be of high clinical relevance. Therefore, we investigated fatigue and underlying pathways in L-thyroxine-using breast cancer patients during chemotherapy.

Methods

Thyroid-stimulating hormone (TSH), L-triiodothyronine (T3), and diurnal salivary cortisol patterns were analyzed in breast cancer patients in the beginning and at the end of adjuvant chemotherapy within the control group (n = 41) of a randomized exercise intervention trial. Additionally, relationships in the exercising group (n = 45) as well as in healthy women (n = 25) were explored. Regression and mediation analyses were performed.

Results

L-Thyroxine use was significantly associated with lower TSH (median = 0.33 mU/l, interquartile range = (0.15–0.48)), whereas patients not using L-thyroxine had TSH comparable to healthy women (0.51 mU/l (0.37–0.74)). T3 significantly declined during chemotherapy in L-thyroxine users but not in non-users. However, the group difference failed statistical significance. L-Thyroxine treatment was significantly associated with increased physical fatigue during chemotherapy (p = 0.004) in the non-exercising group. This association appeared to be partly mediated by TSH. Further, TSH appeared to affect fatigue partly via increased cortisol levels. In the exercise group, there was no significant association between L-thyroxine and fatigue.

Conclusions

L-Thyroxine treatment during chemotherapy might result in hormonal dysregulations that can contribute to increased physical fatigue. Therefore, breast cancer patients on L-thyroxine treatment may need special monitoring of their thyroid levels and of fatigue during chemotherapy and should be encouraged to exercise.

Trial registration: ClinicalTrials.gov NCT01106820.

Keywords

Fatigue Levothyroxine Chemotherapy Thyroid function Cortisol Breast cancer 

Notes

Acknowledgements

We thank Petra Armbrust for study assistance, Christine Niesik, Lin Zielske, Marita Wenzel, and Anett Brendel for technical support in the lab and Dr. Dr. Philipp Zimmer for valuable comments to the manuscript. The foundation “Stiftung Leben mit Krebs” partially supported the intervention programs.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The BEATE and INVEST studies were approved by the Ethics Committee of the University of Heidelberg. 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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Martina E. Schmidt
    • 1
  • Joachim Wiskemann
    • 2
  • Theron Johnson
    • 3
  • Nina Habermann
    • 4
  • Andreas Schneeweiss
    • 2
  • Karen Steindorf
    • 1
  1. 1.Division of Physical Activity, Prevention and CancerGerman Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT)HeidelbergGermany
  2. 2.Division of Medical OncologyUniversity Clinic Heidelberg and National Center for Tumor Diseases (NCT)HeidelbergGermany
  3. 3.Division of Cancer EpidemiologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  4. 4.Genome BiologyEuropean Molecular Biology Laboratory (EMBL)HeidelbergGermany

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