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      Use of thyroid hormones in hypothyroid and euthyroid patients: A 2020 THESIS questionnaire survey of members of the Danish Endocrine Society

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          Abstract

          Purpose

          The standard treatment of hypothyroidism is levothyroxine (LT4), which is available as tablets or soft-gel capsules in Denmark. This study aimed to investigate Danish endocrinologists’ use of thyroid hormones in hypothyroid and euthyroid patients.

          Methods

          An e-mail with an invitation to participate in an online survey investigating practices about substitution with thyroid hormones was sent to all members of the Danish Endocrine Society (DES).

          Results

          Out of 488 eligible DES members, a total of 152 (31.2%) respondents were included in the analysis. The majority (94.1%) of responding DES members use LT4 as the treatment of choice. Other treatment options for hypothyroidism are also used, as 58.6% prescribe combination therapy with liothyronine (LT3) + LT4 in their clinical practice. LT4 + LT3 combination is preferred in patients with persistent symptoms of hypothyroidism despite biochemical euthyroidism on LT4 treatment. Over half of the respondents answered that thyroid hormone therapy is never indicated for euthyroid patients, but 42.1% will consider it for euthyroid infertile women with high antibody levels. In various conditions that could interfere with the absorption of LT4, most responding Danish endocrinologists prefer tablets and do not expect a significant difference when switching from one type of tablet formulation to another.

          Conclusion

          The treatment of choice for hypothyroidism is LT4. Combination therapy with LT4 + LT3 is considered for patients with persistent symptoms. Even in the presence of conditions affecting bioavailability, responding Danish endocrinologists prefer LT4 tablets rather than newer LT4 formulations, such as soft-gel capsules.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s40618-021-01555-y.

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          Most cited references30

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          AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ASSOCIAZIONE MEDICI ENDOCRINOLOGI MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE DIAGNOSIS AND MANAGEMENT OF THYROID NODULES--2016 UPDATE.

          Hossein Gharib, Enrico Papini, Jeffrey R Garber … (2016)
          Thyroid nodules are detected in up to 50 to 60% of healthy subjects. Most nodules do not cause clinically significant symptoms, and as a result, the main challenge in their management is to rule out malignancy, with ultrasonography (US) and fine-needle aspiration (FNA) biopsy serving as diagnostic cornerstones. The key issues discussed in these guidelines are as follows: (1) US-based categorization of the malignancy risk and indications for US-guided FNA (henceforth, FNA), (2) cytologic classification of FNA samples, (3) the roles of immunocytochemistry and molecular testing applied to thyroid FNA, (4) therapeutic options, and (5) follow-up strategy. Thyroid nodule management during pregnancy and in children are also addressed. On the basis of US features, thyroid nodules may be categorized into 3 groups: low-, intermediate-and high-malignancy risk. FNA should be considered for nodules ≤10 mm diameter only when suspicious US signs are present, while nodules ≤5 mm should be monitored rather than biopsied. A classification scheme of 5 categories (nondiagnostic, benign, indeterminate, suspicious for malignancy, or malignant) is recommended for the cytologic report. Indeterminate lesions are further subdivided into 2 subclasses to more accurately stratify the risk of malignancy. At present, no single cytochemical or genetic marker can definitely rule out malignancy in indeterminate nodules. Nevertheless, these tools should be considered together with clinical data, US signs, elastographic pattern, or results of other imaging techniques to improve the management of these lesions. Most thyroid nodules do not require any treatment, and levothyroxine (LT4) suppressive therapy is not recommended. Percutaneous ethanol injection (PEI) should be the first-line treatment option for relapsing, benign cystic lesions, while US-guided thermal ablation treatments may be considered for solid or mixed symptomatic benign thyroid nodules. Surgery remains the treatment of choice for malignant or suspicious nodules. The present document updates previous guidelines released in 2006 and 2010 by the American Association of Clinical Endocrinologists (AACE), American College of Endocrinology (ACE) and Associazione Medici Endocrinologi (AME).
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            The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis.

            Ane Garmendia Madariaga, Silvia Santos Palacios, Francisco Guillén-Grima … (2014)
            Thyroid dysfunction is one of the leading endocrine disorders. Previous data show that about half of the population with thyroid dysfunction remains undiagnosed.
            Article 0 comments Cited 162 times – based on 0 reviews     Review now
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              2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism

              Wilmar M. Wiersinga, Leonidas Duntas, Valentin Fadeyev … (2012)
              Background Data suggest symptoms of hypothyroidism persist in 5–10% of levothyroxine (L-T4)-treated hypothyroid patients with normal serum thyrotrophin (TSH). The use of L-T4 + liothyronine (L-T3) combination therapy in such patients is controversial. The ETA nominated a task force to review the topic and formulate guidelines in this area. Methods Task force members developed a list of relevant topics. Recommendations on each topic are based on a systematic literature search, discussions within the task force, and comments from the European Thyroid Association (ETA) membership at large. Results Suggested explanations for persisting symptoms include: awareness of a chronic disease, presence of associated autoimmune diseases, thyroid autoimmunity per se, and inadequacy of L-T4 treatment to restore physiological thyroxine (T4) and triiodothyronine (T3) concentrations in serum and tissues. There is insufficient evidence that L-T4 + L-T3 combination therapy is better than L-T4 monotherapy, and it is recommended that L-T4 monotherapy remains the standard treatment of hypothyroidism. L-T4 + L-T3 combination therapy might be considered as an experimental approach in compliant L-T4-treated hypothyroid patients who have persistent complaints despite serum TSH values within the reference range, provided they have previously received support to deal with the chronic nature of their disease, and associated autoimmune diseases have been excluded. Treatment should only be instituted by accredited internists/endocrinologists, and discontinued if no improvement is experienced after 3 months. It is suggested to start combination therapy in an L-T4/L-T3 dose ratio between 13:1 and 20:1 by weight (L-T4 once daily, and the daily L-T3 dose in two doses). Currently available combined preparations all have an L-T4/L-T3 dose ratio of less than 13:1, and are not recommended. Close monitoring is indicated, aiming not only to normalize serum TSH and free T4 but also normal serum free T4/free T3 ratios. Suggestions are made for further research. Conclusion L-T4 + L-T3 combination therapy should be considered solely as an experimental treatment modality. The present guidelines are offered to enhance its safety and to counter its indiscriminate use.
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                Author and article information

                Contributors
                K. R. Riis:
                ORCID: http://orcid.org/0000-0003-2679-7153
                Kamilla.Ryom.Riis@rsyd.dk
                Journal
                Journal ID (nlm-ta): J Endocrinol Invest
                Journal ID (iso-abbrev): J Endocrinol Invest
                Title: Journal of Endocrinological Investigation
                Publisher: Springer International Publishing (Cham )
                ISSN (Print): 0391-4097
                ISSN (Electronic): 1720-8386
                Publication date (Electronic): 28 March 2021
                Pages: 1-10
                Affiliations
                [1 ]GRID grid.7143.1, ISNI 0000 0004 0512 5013, Department of Endocrinology, , Odense University Hospital, ; Odense, Denmark
                [2 ]GRID grid.417011.2, ISNI 0000 0004 1769 6825, Division of Endocrinology, , V. Fazzi Hospital, ; Lecce, Italy
                [3 ]IRCCS Orthopedic Institute Galeazzi, Endocrinology Service, Milan, Italy
                [4 ]GRID grid.7122.6, ISNI 0000 0001 1088 8582, Division of Endocrinology, Department of Medicine, Faculty of Medicine, , University of Debrecen, ; Debrecen, Hungary
                [5 ]Department of Endocrinology and Metabolism, Opsedale Regina Apostolorum, Rome, Italy
                [6 ]GRID grid.419334.8, ISNI 0000 0004 0641 3236, Department of Endocrinology, , Royal Victoria Infirmary, ; Newcastle upon Tyne, UK
                Author information
                http://orcid.org/0000-0003-2679-7153
                Article
                Publisher ID: 1555
                DOI: 10.1007/s40618-021-01555-y
                PMC ID: 8004561
                PubMed ID: 33774809
                SO-VID: 49cba852-af83-4257-b5e6-e4241fb7207d
                Copyright © © Italian Society of Endocrinology (SIE) 2021
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 22 January 2021
                Date accepted : 10 March 2021
                Funding
                Funded by: IBSA Institute Biochimique SA
                Funded by: Danish Medicine Agency
                Funded by: The Region of Southern Denmark
                Categories
                Subject: Original Article

                Keywords: levothyroxine,liothyronine,hypothyroidism,euthyroidism,survey,danish endocrine society
                Data availability:
                Keywords: levothyroxine, liothyronine, hypothyroidism, euthyroidism, survey, danish endocrine society

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