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Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options.
Drugs Context 2019; 8:212597DC

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 feed-forward 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.

Authors+Show Affiliations

Department for Nuclear Medicine, Klinikum Lüdenscheid, Paulmannshöherstr. 14, 58515 Lüdenscheid, Germany.North Lakes Clinical, 20 Wheatley Avenue, Ilkley LS29 8PT, UK.Department for Nuclear Medicine, Klinikum Lüdenscheid, Paulmannshöherstr. 14, 58515 Lüdenscheid, Germany.Medical Department I, Endocrinology and Diabetology, Bergmannsheil University Hospitals, Ruhr University of Bochum, Buerkle-de-la-Camp-Platz 1, 44789 Bochum, Germany. Ruhr Center for Rare Diseases (CeSER), Ruhr University of Bochum and Witten/Herdecke University, Alexandrinenstr. 5, 44791 Bochum, Germany.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31516533

Citation

Hoermann, Rudolf, et al. "Individualised Requirements for Optimum Treatment of Hypothyroidism: Complex Needs, Limited Options." Drugs in Context, vol. 8, 2019, p. 212597.
Hoermann R, Midgley JEM, Larisch R, et al. Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options. Drugs Context. 2019;8:212597.
Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2019). Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options. Drugs in Context, 8, p. 212597. doi:10.7573/dic.212597.
Hoermann R, et al. Individualised Requirements for Optimum Treatment of Hypothyroidism: Complex Needs, Limited Options. Drugs Context. 2019;8:212597. PubMed PMID: 31516533.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options. AU - Hoermann,Rudolf, AU - Midgley,John E M, AU - Larisch,Rolf, AU - Dietrich,Johannes W, Y1 - 2019/08/13/ PY - 2019/04/20/received PY - 2019/07/09/revised PY - 2019/07/15/accepted PY - 2019/9/14/entrez KW - LT4 treatment KW - ergodicity KW - hypothyroidism KW - personalised medicine KW - setpoint SP - 212597 EP - 212597 JF - Drugs in context JO - Drugs Context VL - 8 N2 - 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 feed-forward 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. SN - 1745-1981 UR - https://www.unboundmedicine.com/medline/citation/31516533/Individualised_requirements_for_optimum_treatment_of_hypothyroidism:_complex_needs,_limited_options DB - PRIME DP - Unbound Medicine ER -