Treating Hypothyroidism with Thyroxine/Triiodothyronine Combination Therapy in Denmark: Following Guidelines or Following Trends?
Open accessAbstract
Background: Five to ten percent of patients with hypothyroidism describe persistent symptoms despite being biochemically well regulated on levothyroxine (L-T 4). Thyroxine (T 4)/triiodothyronine (T 3) combination therapy [L-T 4/liothyronine (L-T 3) 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 4/T 3 combination therapy as compared to L-T 4 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 4/T 3 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 3 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 4/T 3 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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The four most prevalent areas of persistent complaints in LT4-treated hypothyroid patients are fatigue or energy levels (80% to 90%), weight management (70% to 75%), memory (60% to 80%), and mood (40% to 50%).
“most frequent are complaints about energy levels and fatigue (80% to 90%), weight management (70% to 75%), memory (60% to 80%), and mood (40% to 50%).”
From T4+T3 Combination Therapy: An Unsolved Problem of Increasing Magnitude and Complexity (2021) · cites this paper as [30]
The Results symptom table reports lack of energy (87%) and weight problems (75%) within the claimed ranges, but being tired (91%), cognitive problems (83%), and depression (39%) fall outside them. It also lists musculoskeletal symptoms (76%) as more prevalent than weight problems or depression. These figures describe surveyed patients before they began T4/T3 combination therapy, not LT4-treated patients generally. (LLM, conf=0.90)
Experimental — accuracy not yet measuredAn observational study derived from pharmacy data showed that following publication of the European Thyroid Association Guidelines, there was a trend for increasing numbers of LT3 and DTE prescriptions at a specific pharmacy in Denmark.
“An observational study derived from pharmacy data did show that following the publication of the European Thyroid Association Guidelines (1), which stated that combination therapy could be considered under specific circumstances, there was a trend for increasing numbers of LT3 and DTE prescriptions to be received at a specific pharmacy in Denmark (34).”
From Short-Term Time Trends in Prescribing Therapy for Hypothyroidism: Results of a Survey of American Thyroid Association Members (2019) · cites this paper as [34]
The Results (page unavailable) report that Glostrup Pharmacy’s sales of both L-T3 and desiccated thyroid increased during 2013, supporting the claimed trend. The pharmacy data count packages sold, however, not prescriptions received; the paper says exact prescription data could not be extracted. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe median number of persistent symptoms per LT4-treated hypothyroid patient is 7 (IQR, 5 to 8), and two-thirds of patients have ≥6 different symptoms.
“The median number of symptoms per participant was 7 (interquartile range [IQR], 5 to 8); as many as 69% of patients had ≥6 different symptoms.”
From T4+T3 Combination Therapy: An Unsolved Problem of Increasing Magnitude and Complexity (2021) · cites this paper as [30]
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- Authors
- Michaelsson, L. F., Medici, B. B., la Cour, J. L., Selmer, C., Røder, M., Perrild, H., Knudsen, N., Faber, J., & Nygaard, B.
- Affiliations
- University of Copenhagen (DK)
- 1Department of Endocrinology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
- ORCID
- Venue
- European Thyroid Journal
- Publisher
- Bioscientifica
- Published
- 2015-08-14
- Volume
- 4
- Issue
- 3
- Pages
- 174-180
- ISSN
- 2235-0640 (ISSN-L)
- 2235-0802
- PMC
- PMC4637515
- OpenAlex
- W2138557474
- Cited by
- 57
- References
- 14
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 7 · 2023: 4 · 2022: 7 · 2021: 8 · 2020: 6 · 2019: 8 · 2018: 8 · 2017: 4
- FWCI
- 3.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Thyroid Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- hypothyroidism, levothyroxine, triiodothyronine, desiccated thyroid, overtreatment, prescribing patterns, patient forums
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