Institute of Automatic Control, Leibniz University Hannover, Hannover, Germany.
Diabetes, Endocrinology and Metabolism Section, Department of Internal Medicine I, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
Front Endocrinol (Lausanne). 2022 Jun 24;13:884018. doi: 10.3389/fendo.2022.884018. eCollection 2022.
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 -) monotherapy or a liothyronine/levothyroxine (-/-) combined therapy is more suitable to treat hypothyroidism. Third, the optimal intake frequency of -/- 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 -/-. 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 -/- combined therapy is slightly better (in terms of the achieved hormone concentrations) to treat hypothyroidism than the - monotherapy. In case of a specific genetic variant, namely genotype CC in polymorphism rs2235544 of gene , the simulation results suggest that the - monotherapy is better to treat hypothyroidism. In turn, when genotype AA is considered, the -/- 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 gene is considered, the outcome of the -/- 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 - could be the best trade-off between stable hormone concentrations and inconveniences for the patient.
在本文中，我们解决了为甲状腺功能减退症患者制定最佳甲状腺激素替代策略的问题。这是具有挑战性的，原因如下。首先，很难确定导致患者血清甲状腺激素浓度正常化的正确剂量。其次，尚不清楚左旋甲状腺素（）单药治疗还是三碘甲状腺原氨酸/左旋甲状腺素（/-）联合治疗更适合治疗甲状腺功能减退症。第三，/-的最佳摄入频率尚不清楚。我们通过扩展垂体-甲状腺反馈环的数学模型来解决这些问题，使其能够考虑口服/-。采用模型预测控制器（MPC）来确定每种治疗类型的甲状腺激素浓度的最佳剂量。结果表明，与 - 单药治疗相比，/- 联合治疗对治疗甲状腺功能减退症略好（就达到的激素浓度而言）。在特定遗传变异的情况下，即基因 rs2235544 多态性中的基因型 CC，模拟结果表明 - 单药治疗更适合治疗甲状腺功能减退症。相反，当考虑基因型 AA 时，/- 联合治疗更适合治疗甲状腺功能减退症。此外，当考虑基因中的多态性 rs225014（也称为 c.274A>G 或 p.Thr92Ala）的基因型 CC 时，/- 联合治疗在稳态激素浓度方面的结果更好（对于三碘甲状腺原氨酸设定点在上限健康个体的参考范围）。最后，结果表明，每天两次摄入 - 可能是稳定激素浓度和患者不便之间的最佳折衷方案。
