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Luba Freja Michaelsson Department of Endocrinology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark

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Bjarke Borregaard Medici Department of Endocrinology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark

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Jeppe Lerche la Cour Department of Endocrinology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Christian Selmer Department of Endocrinology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark

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Michael Røder Department of Medicine, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
Division of Pharmacies and Reimbursement, Danish Health and Medicines Authority, Copenhagen, Denmark

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Hans Perrild Department of Endocrinology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark

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Nils Knudsen Department of Endocrinology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark

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Jens Faber Department of Endocrinology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Birte Nygaard Department of Endocrinology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark

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Background: Five to ten percent of patients with hypothyroidism describe persistent symptoms despite being biochemically well regulated on levothyroxine (L-T<sub>4</sub>). Thyroxine (T<sub>4</sub>)/triiodothyronine (T<sub>3</sub>) combination therapy [L-T<sub>4</sub>/liothyronine (L-T<sub>3</sub>) or desiccated thyroid] are still regarded as experimental with no evidence of superior effect on persistent symptoms according to meta-analyses. However, some randomized controlled trials have demonstrated patients' preference for T<sub>4</sub>/T<sub>3</sub> combination therapy as compared to L-T<sub>4</sub> monotherapy. In 2013, attention to combination therapy increased in Denmark after a patient published a book describing her experiences with hypothyroidism and treatment. Objective: To investigate current Danish trends in the use of T<sub>4</sub>/T<sub>3</sub> combination therapy. Methods: We used an Internet-based questionnaire, distributed as a link via two Danish patient fora. Further, information was obtained from the Division of Pharmacies and Reimbursement at the Danish Health and Medicines Authority and from the only pharmacy in Denmark producing desiccated thyroid and L-T<sub>3</sub> tablets. Results: A total of 384 patients answered the questionnaire, and 293 responders were included. Sixty-nine percent of the responders had six or more symptoms, and 84% reported a treatment effect. Forty-four percent of the responders received their prescriptions from general practitioners; 50% received desiccated thyroid and 28% reported that they adjust their dose themselves. Responders followed by general practitioners more frequently received desiccated thyroid and adjusted their dose themselves. Conclusions: Increased media focus has changed the prescription pattern of thyroid hormones; European guidelines on T<sub>4</sub>/T<sub>3</sub> combination therapy are not always followed in Denmark and many patients adjust their medication themselves and may therefore be at risk of overtreatment.

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Line Tang Møllehave Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark

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Nils Knudsen Department of Endocrinology, Bispebjerg University Hospital, University of Copenhagen, Denmark

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Allan Linneberg Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Inge Bülow Pedersen Department of Endocrinology and Medicine, Aalborg University Hospital, Aalborg, Denmark

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Gitte Ravn-Haren Research Group for Risk Benefit, National Food Institute, Technical University of Denmark, Lyngby, Denmark

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Anja Lykke Madsen Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark

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Allan Carlé Department of Endocrinology and Medicine, Aalborg University Hospital, Aalborg, Denmark

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Charlotte Cerqueira The Danish Clinical Quality Program – National Clinical Registries (RKKP), Denmark

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Anne Krejbjerg Department of Oncology, Aalborg University Hospital, Aalborg, Denmark

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Lone Banke Rasmussen Independent researcher, Klemensker, Denmark

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Lars Ovesen Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark

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Hans Perrild Department of Endocrinology, Bispebjerg University Hospital, University of Copenhagen, Denmark

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Lena Bjergved Sigurd Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Internal Medicine, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark

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Betina Heinsbæk Thuesen Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark

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Pernille Vejbjerg Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark

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Torben Jørgensen Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Due to mild-to-moderate iodine deficiency in Denmark, health authorities initiated a voluntary iodine fortification (IF) program in 1998, which became mandatory in 2000. In line with recommendations from the World Health Organization, the Danish investigation on iodine intake and thyroid disease (DanThyr) was established to monitor the effect on thyroid health and disease. The program involved different study designs and followed two Danish sub-populations in the years before IF and up till 20 years after. Results showed that the IF was successfully implemented and increased the level of iodine intake from mild–moderate iodine deficiency to low adequacy. The level of thyroglobulin and thyroid volume decreased following IF, and there was an indication of fewer thyroid nodules. The incidence of hyperthyroidism increased transiently following IF but subsequently decreased below the pre-fortification level. Conversely, thyroid-stimulating hormone levels and the prevalence of thyroid autoimmunity increased along with an increase in the incidence of hypothyroidism. These trends were mirrored in the trends in treatments for thyroid disease. Most differences in thyroid health and disease between regions with different iodine intake levels before IF attenuated. This review illustrates the importance of a monitoring program to detect both beneficial and adverse effects and exemplifies how a monitoring program can be conducted when a nationwide health promotion program – as IF – is initiated.

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