Details
| Original language | English |
|---|---|
| Article number | 884018 |
| Number of pages | 13 |
| Journal | Frontiers in Endocrinology |
| Volume | 13 |
| Publication status | Published - 24 Jun 2022 |
Abstract
In this paper, we address the problem of optimal thyroid hormone replacement strategy development for hypothyroid patients. This is challenging for the following reasons. First, it is difficult to determine the correct dosage leading to normalized serum thyroid hormone concentrations of a patient. Second, it remains unclear whether a levothyroxine L-T 4) monotherapy or a liothyronine/levothyroxine (L-T 3/L-T 4) combined therapy is more suitable to treat hypothyroidism. Third, the optimal intake frequency of L-T 3/L-T 4 is unclear. We address these issues by extending a mathematical model of the pituitary-thyroid feedback loop to be able to consider an oral intake of L-T 3/L-T 4. A model predictive controller (MPC) is employed to determine optimal dosages with respect to the thyroid hormone concentrations for each type of therapy. The results indicate that the L-T 3/L-T 4 combined therapy is slightly better (in terms of the achieved hormone concentrations) to treat hypothyroidism than the L-T 4 monotherapy. In case of a specific genetic variant, namely genotype CC in polymorphism rs2235544 of gene DIO1, the simulation results suggest that the L-T 4 monotherapy is better to treat hypothyroidism. In turn, when genotype AA is considered, the L-T 3/L-T 4 combined therapy is better to treat hypothyroidism. Furthermore, when genotype CC of polymorphism rs225014 (also referred to as c.274A>G or p.Thr92Ala) in the DIO2 gene is considered, the outcome of the L-T 3/L-T 4 combined therapy is better in terms of the steady-state hormone concentrations (for a triiodothyronine setpoint at the upper limit of the reference range of healthy individuals). Finally, the results suggest that two daily intakes of L-T 3 could be the best trade-off between stable hormone concentrations and inconveniences for the patient.
Keywords
- automatic control, combined therapy, mathematical modeling, model predictive control, monotherapy, thyroid homeostasis
ASJC Scopus subject areas
- Medicine(all)
- Endocrinology, Diabetes and Metabolism
Sustainable Development Goals
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In: Frontiers in Endocrinology, Vol. 13, 884018, 24.06.2022.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Optimal Hormone Replacement Therapy in Hypothyroidism
T2 - A Model Predictive Control Approach
AU - Wolff, Tobias M.
AU - Dietrich, Johannes W.
AU - Müller, Matthias A.
N1 - Funding Information: This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 948679).
PY - 2022/6/24
Y1 - 2022/6/24
N2 - In this paper, we address the problem of optimal thyroid hormone replacement strategy development for hypothyroid patients. This is challenging for the following reasons. First, it is difficult to determine the correct dosage leading to normalized serum thyroid hormone concentrations of a patient. Second, it remains unclear whether a levothyroxine L-T 4) monotherapy or a liothyronine/levothyroxine (L-T 3/L-T 4) combined therapy is more suitable to treat hypothyroidism. Third, the optimal intake frequency of L-T 3/L-T 4 is unclear. We address these issues by extending a mathematical model of the pituitary-thyroid feedback loop to be able to consider an oral intake of L-T 3/L-T 4. A model predictive controller (MPC) is employed to determine optimal dosages with respect to the thyroid hormone concentrations for each type of therapy. The results indicate that the L-T 3/L-T 4 combined therapy is slightly better (in terms of the achieved hormone concentrations) to treat hypothyroidism than the L-T 4 monotherapy. In case of a specific genetic variant, namely genotype CC in polymorphism rs2235544 of gene DIO1, the simulation results suggest that the L-T 4 monotherapy is better to treat hypothyroidism. In turn, when genotype AA is considered, the L-T 3/L-T 4 combined therapy is better to treat hypothyroidism. Furthermore, when genotype CC of polymorphism rs225014 (also referred to as c.274A>G or p.Thr92Ala) in the DIO2 gene is considered, the outcome of the L-T 3/L-T 4 combined therapy is better in terms of the steady-state hormone concentrations (for a triiodothyronine setpoint at the upper limit of the reference range of healthy individuals). Finally, the results suggest that two daily intakes of L-T 3 could be the best trade-off between stable hormone concentrations and inconveniences for the patient.
AB - In this paper, we address the problem of optimal thyroid hormone replacement strategy development for hypothyroid patients. This is challenging for the following reasons. First, it is difficult to determine the correct dosage leading to normalized serum thyroid hormone concentrations of a patient. Second, it remains unclear whether a levothyroxine L-T 4) monotherapy or a liothyronine/levothyroxine (L-T 3/L-T 4) combined therapy is more suitable to treat hypothyroidism. Third, the optimal intake frequency of L-T 3/L-T 4 is unclear. We address these issues by extending a mathematical model of the pituitary-thyroid feedback loop to be able to consider an oral intake of L-T 3/L-T 4. A model predictive controller (MPC) is employed to determine optimal dosages with respect to the thyroid hormone concentrations for each type of therapy. The results indicate that the L-T 3/L-T 4 combined therapy is slightly better (in terms of the achieved hormone concentrations) to treat hypothyroidism than the L-T 4 monotherapy. In case of a specific genetic variant, namely genotype CC in polymorphism rs2235544 of gene DIO1, the simulation results suggest that the L-T 4 monotherapy is better to treat hypothyroidism. In turn, when genotype AA is considered, the L-T 3/L-T 4 combined therapy is better to treat hypothyroidism. Furthermore, when genotype CC of polymorphism rs225014 (also referred to as c.274A>G or p.Thr92Ala) in the DIO2 gene is considered, the outcome of the L-T 3/L-T 4 combined therapy is better in terms of the steady-state hormone concentrations (for a triiodothyronine setpoint at the upper limit of the reference range of healthy individuals). Finally, the results suggest that two daily intakes of L-T 3 could be the best trade-off between stable hormone concentrations and inconveniences for the patient.
KW - automatic control
KW - combined therapy
KW - mathematical modeling
KW - model predictive control
KW - monotherapy
KW - thyroid homeostasis
UR - http://www.scopus.com/inward/record.url?scp=85134055484&partnerID=8YFLogxK
U2 - 10.3389/fendo.2022.884018
DO - 10.3389/fendo.2022.884018
M3 - Article
VL - 13
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
SN - 1664-2392
M1 - 884018
ER -