Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options

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Abstract

Levothyroxine (LT4) therapy has a long history, a well-defined pharmacological profile and a favourable safety record in the alleviation of hypothyroidism. However, questions remain in defining the threshold for the requirement of treatment in patients with subclinical hypothyroidism, assessing the dose adequacy of the drug, and selecting the best treatment mode (LT4 monotherapy versus liothyronine [LT3]/LT4 combinations) for subpopulations with persisting complaints. Supplied as a prodrug, LT4 is enzymatically converted into the biologically more active thyroid hormone, triiodothyronine (T3). Importantly, tetraiodothyronine (T4) to T3 conversion efficiency may be impaired in patients receiving LT4, resulting in a loss of thyroid-stimulating hormone (TSH)-mediated feedforward control of T3, alteration of the interlocking equilibria between serum concentrations of TSH, free thyroxine (FT4), and free triiodothyonine (FT3), and a decrease in FT3 to FT4 ratios. This downgrades the value of the TSH reference system derived in thyroid health for guiding the replacement dose in the treatment situation. Individualised conditionally defined setpoints may therefore provide appropriate biochemical targets to be clinically tested, together with a stronger focus on clinical presentation and future endpoint markers of tissue thyroid state. This cautionary note encompasses the use of aggregated statistical data from clinical trials which are not safely applicable to the individual level of patient care under these circumstances.

Keywords: ergodicity, hypothyroidism, LT4 treatment, personalised medicine, setpoint.

Citation: Hoermann R, Midgley JEM, Larisch R, Dietrich JW. Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options. Drugs in Context 2019; 8: 212597. DOI: 10.7573/dic.212597

Contributions: RH drafted the manuscript. JEM, RL and JWD contributed additional ideas, text passages, edits, and references. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosure and potential conflicts of interest: JWD is co-owner of the intellectual property rights for the patent ‘System and Method for Deriving Parameters for Homeostatic Feedback Control of an Individual’ (Singapore Institute for Clinical Sciences, Biomedical Sciences Institutes, Application Number 201208940-5, WIPO number WO/2014/088516). All other authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at https://www.drugsincontext.com/wp-content/uploads/2019/08/dic.212597-COI.pdf

Acknowledgments: None.

Funding declaration: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Copyright: Copyright © 2019 Hoermann R, Midgley JEM, Larisch R, Dietrich JW. https://doi.org/10.7573/dic.212597. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2019 Hoermann R, Midgley JEM, Larisch R, Dietrich JW. Published by Drugs in Context under Creative
Commons License Deed CC BY NC ND 4.0.

Article URL: https://www.drugsincontext.com/individualised-requirements-for-optimum-treatment-of-hypothyroidism:-complex-needs,-limited-options

Correspondence: Rudolf Hoermann, MD, PhD, Klinikum Lüdenscheid, Paulmannshöhler Str 14, D-58515 Lüdenscheid, Germany. rudolf.hoermann@gmail.com

Provenance: invited; externally peer reviewed.

Submitted: 20 April 2019; Peer review comments to author: 2 July 2019; Revised manuscript received: 9 July 2019; Accepted: 15 July 2019; Publication date: 13 August 2019.

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