Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options
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...
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2019-08-01
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doaj-7a37aa97e1a04b3d83a5cac22483a1c32020-11-24T21:55:28ZengBioExcel Publishing LtdDrugs in Context1740-43981740-43982019-08-01811810.7573/dic.212597Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited optionsRudolf HoermannJohn E M MidgleyRolf LarischJohannes W DietrichLevothyroxine (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.https://www.drugsincontext.com/individualised-requirements-for-optimum-treatment-of-hypothyroidism:-complex-needs,-limited-options/ergodicityhypothyroidismLT4 treatmentpersonalised medicinesetpoint |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rudolf Hoermann John E M Midgley Rolf Larisch Johannes W Dietrich |
spellingShingle |
Rudolf Hoermann John E M Midgley Rolf Larisch Johannes W Dietrich Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options Drugs in Context ergodicity hypothyroidism LT4 treatment personalised medicine setpoint |
author_facet |
Rudolf Hoermann John E M Midgley Rolf Larisch Johannes W Dietrich |
author_sort |
Rudolf Hoermann |
title |
Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options |
title_short |
Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options |
title_full |
Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options |
title_fullStr |
Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options |
title_full_unstemmed |
Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options |
title_sort |
individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options |
publisher |
BioExcel Publishing Ltd |
series |
Drugs in Context |
issn |
1740-4398 1740-4398 |
publishDate |
2019-08-01 |
description |
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. |
topic |
ergodicity hypothyroidism LT4 treatment personalised medicine setpoint |
url |
https://www.drugsincontext.com/individualised-requirements-for-optimum-treatment-of-hypothyroidism:-complex-needs,-limited-options/ |
work_keys_str_mv |
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