USE OF THYROID HORMONES IN EUTHYROID PATIENTS WITH UNEXPLAINED FATIGUE: ANALYSES OF AGGREGATE DATA FROM EUROPEAN NATIONAL SURVEYS OF PROFESSIONAL ENDOCRINE SOCIETY MEMBERS

Tomasz Bednarczuk^1*Aleksandra Sugier^1*Roberto Attanasio²Endre V. Nagy³Roberto Negro⁴Enrico Papini⁵Miloš Žarković⁶Ersin Akarsu⁷Maria Alevizaki⁸Göksun Ayvaz⁹Biljana Nedeljković Beleslin⁶Eszter Berta³Miklós Bodor³Anna-Maria Borissova¹⁰Mihail Boyanov^11,12Camille Buffet¹³Maria-Cristina Burlacu¹⁴Chagit Cohen¹⁵Jasmina Ćirić⁶Juan Díez^16,17,18Harald Dobnig¹⁹Valentin Fadeyev²⁰Benjamin C.T. Field²¹Eric Fliers²²Dagmar Führer-Sakel²³Jacob Frølich²⁴Juan Carlos Galofre^25,26Tommi Hakala²⁷Jan Jiskra²⁸Peter Kopp²⁹Michael Krebs³⁰Michal Kršek²⁸Martin Kužma³¹Ivica Lazúrová³²Laurence Leenhardt¹³Stephen Ludgate^33,34Vitaliy Luchytskiy³⁵Anne McGowan^33,34Miguel Melo³⁶Saara Metso²⁷Carla Moran^37,38,39Tatyana MORGUNOVA²⁰Dan Alexandru Niculescu⁴⁰Bozidar Peric⁴¹Tereza Planck⁴²Catalina Poiana⁴⁰Francisca Puga⁴³Eyal Robenshtok⁴⁴Patrick Rosselet⁴⁵Marek Ruchala⁴⁶Kamilla Ryom Riis²⁴Alla Shepelkevich⁴⁷Mykola Tronko⁴⁸David Unuane⁴⁹Irfan Vardarli^50,51W Edward Visser⁵²Andromachi Vryonidou⁵³Younes R Younes⁵⁴Elena Yurenya⁵⁵Petros Perros⁵⁶Laszlo Hegedüs²⁴

• ¹Medical University of Warsaw, Warsaw, Poland
• ²Scientific Committee Associazione Medici Endocrinologi, Udine, Italy
• ³Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
• ⁴Department of Experimental Medicine, University of Salento and Division of Endocrinology V. Fazzi Hospital, Lecce, Italy
• ⁵Department of Endocrinology and Metabolism, Regina Apostolorum Hospital, Lifenet Health Group, Albano Laziale, Rome, Italy
• ⁶Faculty of Medicine, University of Belgrade, Belgrade, Serbia
• ⁷Department of Internal Medicine, Division of Endocrinology, Faculty of Medicine, Gaziantep University, Gaziantep, Türkiye
• ⁸Endocrine Unit and Diabetes Centre, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
• ⁹Koru Ankara Hospital, Department of Endocrinology and Metabolism, Ankara, Türkiye
• ¹⁰Clinic of Endocrinology and Metabolism, University Hospital “Sofiamed”, Medical Faculty, Sofia University “Saint Kliment Ohridski", Sofia, Bulgaria
• ¹¹Clinic of Endocrinology and Metabolism, University Hospital “Alexandrovska”, Sofia, Bulgaria
• ¹²Department of Internal Medicine, Medical University, Sofia, Bulgaria
• ¹³Sorbonne Universitè, GRC n 16, GRC Thyroid Tumors, Thyroid Diseases and Endocrine Tumor Department, AP-HP, Hôpital Pitié-Salpêtriére, Paris, France
• ¹⁴Department of Endocrinology and Nutrition, Cliniques Universitaires St-Luc, Université Catholique de Louvain, Brussels, Belgium
• ¹⁵Rabin Medical Center, Tel-Aviv University, Tel-Aviv, Israel
• ¹⁶Hospital Universitario Puerta de Hierro Majadahonda, Department of Endocrinology, Madrid, Spain
• ¹⁷Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana, Majadahonda, Madrid, Spain
• ¹⁸Universidad Autónoma de Madrid, Department of Medicine, Madrid, Spain
• ¹⁹Thyroid practice and specialty practice for thyroid radiofrequency ablation, Kumberg, Austria
• ²⁰Department of Endocrinology No. 1, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
• ²¹Section of Clinical Medicine, Faculty of Health & Medical Sciences, University of Surrey, Guildford, United Kingdom
• ²²Department of Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
• ²³Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University-Duisburg-Essen, Essen, Germany
• ²⁴Department of Endocrinology, Odense University Hospital, Odense, Denmark
• ²⁵Department of Endocrinology, Clínica Universidad de Navarra, Pamplona, Spain
• ²⁶Instituto de Investigacion Sanitaria de Navarra, Pamplona, Spain
• ²⁷Department of Surgery, Tampere University Hospital, Tampere, Finland
• ²⁸3rd Department of Medicine, 1st Faculty of Medicine, Charles University, General University Hospital, Prague, Czechia
• ²⁹Division of Endocrinology, Diabetology and Metabolism, University of Lausanne, Lausanne, Switzerland
• ³⁰Internal Medicine III, Division of Endocrinology, Medical University of Vienna, Vienna, Austria
• ³¹5th Department of Internal Medicine, Medical Faculty of Comenius University and University Hospital, Bratislava, Slovakia
• ³²P.J. Šafárik University Košice, 1st Department of Internal Medicine of the Medical Faculty, Košice, Slovakia
• ³³The School of Medicine, Trinity College Dublin, The University of Dublin, Dublin, Ireland
• ³⁴Robert Graves Institute, Tallaght University Hospital, Dublin, Ireland
• ³⁵Department of Reproductive Endocrinogy, Institute of Endocrinology and Metabolism named after V.P. Komissarenko, National Academy of Medical Science of Ukraine, Kyiv, Ukraine
• ³⁶Department of Endocrinology, Diabetes and Metabolism Coimbra Local Health Unit; Medical Faculty, University of Coimbra, Coimbra, Portugal
• ³⁷Diabetes & Endocrinology Section, Beacon Hospital, Dublin, Ireland
• ³⁸School of Medicine, University College Dublin, Dublin, Ireland
• ³⁹Endocrine Department, St Vincent’s University Hospital, Dublin, Ireland
• ⁴⁰Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
• ⁴¹Department of Endocrinology, Diabetes and Metabolic Diseases "Mladen Sekso", University Hospital Center "Sisters of Mercy", Zagreb, Croatia
• ⁴²Department of Endocrinology, Skåne University Hospital, Malmö, Sweden
• ⁴³Serviço de Endocrinologia, Diabetes e Metabolismo, ULS São João, Porto, Portugal
• ⁴⁴Endocrinology Institute, Rabin Medical Center, Gray Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel
• ⁴⁵Cabinet Médical 2, rue Bellefontaine, Lausanne, Switzerland
• ⁴⁶Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland
• ⁴⁷Belarusian State Medical University, Department of Endocrinology, Minsk, Belarus
• ⁴⁸V.P. Komissarenko Institute of Endocrinology and Metabolism, National Academy of Medical Science of Ukraine, Kyiv, Ukraine
• ⁴⁹Department of Internal Medicine, Endocrine Unit, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium
• ⁵⁰Department of Medicine I, Klinikum Vest GmbH Knappschaftskrankenhaus Recklinghausen, Academic Hospital, Ruhr-University Bochum, Recklinghausen, Germany
• ⁵¹5th Medical Department, Division of Endocrinology and Diabetes, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
• ⁵²Rotterdam Thyroid Center, Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands
• ⁵³Department of Endocrinology and Diabetes Centre, Hellenic Red Cross Hospital, Athens, Greece
• ⁵⁴East Surrey Hospital, Surrey & Sussex Healthcare NHS Trust, Redhill, United Kingdom
• ⁵⁵Minsk Endocrinology Medical Center, Minsk, Belarus
• ⁵⁶Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom

Background: Managing patients with fatigue is a clinical challenge. Because fatigue is often reported in hypothyroidism, thyroid hormone (TH) therapy may sometimes be incorrectly considered for biochemically euthyroid individuals. This study aimed to evaluate the prevalence and determinants of this practice in different European countries. Methods: We analysed aggregate data from the THESIS (Treatment of Hypothyroidism in Europe by Specialists: an International Survey) online survey. We analysed responses from 5,695 members of 28 national endocrine/thyroid societies’ specialists to the statement: “Thyroid hormones may be indicated in biochemically euthyroid patients with unexplained fatigue”. Results: Overall, 7.5% (426/5695) of respondents indicated that TH therapy might be considered for euthyroid patients with unexplained fatigue. The proportion of positive responses varied widely across different countries (between 1.1% in Switzerland and 29.3% in Serbia; p=2 ×10-16) and regions (between 4.7% in Western Europe and 8.7% in Western Asia or 8.8% in Eastern Europe; p=0.004). TH were more frequently prescribed for unexplained fatigue by male respondents (Odds Ratio, OR 1.45, 95% CI 1.18-1.78) and physicians practicing in private practice (OR 1.27, 95% CI 1.02-1.58), and less frequently by endocrinologists (OR 0.62, 95% CI 0.46-0.83). Conclusion: A small, yet not negligible percentage of European thyroid-focused physicians consider using TH for euthyroid patients with unexplained fatigue, with significant variations based on geographic, demographic, and practice-related factors. Using levothyroxine and/or liothyronine in such cases lacks evidence and may partially contribute to the concerning overuse of TH therapy.