Martina E Schmidt1, Joachim Wiskemann2, Theron Johnson3, Nina Habermann4, Andreas Schneeweiss2, Karen Steindorf5. 1. Division of Physical Activity, Prevention and Cancer, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. m.schmidt@dkfz.de. 2. Division of Medical Oncology, University Clinic Heidelberg and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. 3. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. 4. Genome Biology, European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117, Heidelberg, Germany. 5. Division of Physical Activity, Prevention and Cancer, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, 69120, Heidelberg, Germany.
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 onL-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.
RCT Entities:
PURPOSE:L-Thyroxine is one of the most commonly prescribed drugs and accordingly used by many breast cancerpatients 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 cancerpatients during chemotherapy. METHODS:Thyroid-stimulating hormone (TSH), L-triiodothyronine (T3), and diurnal salivary cortisol patterns were analyzed in breast cancerpatients 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 cancerpatients 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.
Entities:
Keywords:
Breast cancer; Chemotherapy; Cortisol; Fatigue; Levothyroxine; Thyroid function
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