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      Liothyronine and levothyroxine prescribing in England: A comprehensive survey and evaluation

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          Abstract

          Introduction

          The approach to thyroid hormone replacement varies across centres, but the extent and determinants of variation is unclear. We evaluated geographical variation in levothyroxine (LT4) and liothyronine (LT3) prescribing across General Practices in England and analysed the relationship of prescribing patterns to clinical and socioeconomic factors.

          Methods

          Data was downloaded from the NHS monthly General Practice Prescribing Data in England for the period 2011‐2020.

          Results

          The study covered a population of 19.4 million women over 30 years of age, attending 6,660 GP practices and being provided with 33.7 million prescriptions of LT4 and LT3 at a total cost of £90million/year. Overall, 0.5% of levothyroxine treated patients continue to receive liothyronine. All Clinical Commission Groups (CCGs) in England continue to have at least one liothyronine prescribing practice and 48.5% of English general practices prescribed liothyronine in 2019‐2020. Factors strongly influencing more levothyroxine prescribing (model accounted for 62% of variance) were the CCG to which the practice belonged and the proportion of people with diabetes registered on the practice list plus antidepressant prescribing, with socioeconomic disadvantage associated with less levothyroxine prescribing. Whereas factors that were associated with increased levels of liothyronine prescribing (model accounted for 17% of variance), were antidepressant prescribing and % of type 2 diabetes mellitus individuals achieving HbA1c control of 58 mmol/mol or less. Factors that were associated with reduced levels of liothyronine prescribing included smoking and higher obesity rates.

          Conclusion

          In spite of strenuous attempts to limit prescribing of liothyronine in general practice a significant number of patients continue to receive this therapy, although there is significant geographical variation in the prescribing of this as for levothyroxine, with specific general practice and CCG‐related factors influencing prescribing of both levothyroxine and liothyronine across England.

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          Most cited references12

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          Global epidemiology of hyperthyroidism and hypothyroidism

          Thyroid hormones are essential for growth, neuronal development, reproduction and regulation of energy metabolism. Hypothyroidism and hyperthyroidism are common conditions with potentially devastating health consequences that affect all populations worldwide. Iodine nutrition is a key determinant of thyroid disease risk; however, other factors, such as ageing, smoking status, genetic susceptibility, ethnicity, endocrine disruptors and the advent of novel therapeutics, including immune checkpoint inhibitors, also influence thyroid disease epidemiology. In the developed world, the prevalence of undiagnosed thyroid disease is likely falling owing to widespread thyroid function testing and relatively low thresholds for treatment initiation. However, continued vigilance against iodine deficiency remains essential in developed countries, particularly in Europe. In this report, we review the global incidence and prevalence of hyperthyroidism and hypothyroidism, highlighting geographical differences and the effect of environmental factors, such as iodine supplementation, on these data. We also highlight the pressing need for detailed epidemiological surveys of thyroid dysfunction and iodine status in developing countries.
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            Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement.

            A number of recent advances in our understanding of thyroid physiology may shed light on why some patients feel unwell while taking levothyroxine monotherapy. The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care. This document is intended to inform clinical decision-making on thyroid hormone replacement therapy; it is not a replacement for individualized clinical judgment.
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              2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism

              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
                adrian.heald@manchester.ac.uk
                Journal
                Int J Clin Pract
                Int J Clin Pract
                10.1111/(ISSN)1742-1241
                IJCP
                International Journal of Clinical Practice
                John Wiley and Sons Inc. (Hoboken )
                1368-5031
                1742-1241
                06 July 2021
                September 2021
                : 75
                : 9 ( doiID: 10.1111/ijcp.v75.9 )
                : e14228
                Affiliations
                [ 1 ] Res Consortium Andover UK
                [ 2 ] Thyroid Research Group Systems Immunity Research Institute Cardiff University School of Medicine Cardiff UK
                [ 3 ] The School of Medicine Manchester Academic Health Sciences Centre University of Manchester Manchester UK
                [ 4 ] Department of Endocrinology and Diabetes Salford Royal Hospital Salford UK
                Author notes
                [*] [* ] Correspondence

                Adrian H. Heald, Department of Endocrinology and Diabetes, Salford Royal Hospital, Salford, UK.

                Email: adrian.heald@ 123456manchester.ac.uk

                Author information
                https://orcid.org/0000-0002-0491-7823
                https://orcid.org/0000-0002-9537-4050
                Article
                IJCP14228
                10.1111/ijcp.14228
                9285455
                33864324
                2e68809e-a181-4ba5-a15d-5764f6a38a0c
                © 2021 The Authors. International Journal of Clinical Practice published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 28 March 2021
                : 06 January 2021
                : 12 April 2021
                Page count
                Figures: 4, Tables: 1, Pages: 8, Words: 3859
                Categories
                Original Paper
                Original Papers
                Metabolism & Endocrinology
                Custom metadata
                2.0
                September 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.7 mode:remove_FC converted:15.07.2022

                Medicine
                Medicine

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