This upcoming paper is joined with ours in the same edition of Frontiers.
However, do not judge it on a personal level. It simply shows, against different situations, a general trend which either supports or does not the use of combined therapy. It indicates optimum dosing schedules for T3. It is therefore to be looked at as a statistical model, suitable for promoting optimum dosing and what with. Within the limits therefore, individual trials can be made by a person to find their optimum treatment regimen. Note that combined therapy is generally somewhat better than T4 only. Also note that mutations in the DIO2 gene have an effect on this.
The paper will emerge together with ours - based on equivalent modelling techniques.
Optimal hormone replacement therapy in hypothyroidism - a model predictive control approach
Tobias M. Wolff1*, Johannes W. Dietrich2, 3, 4 and Matthias A. Müller1
1Institute of Automatic Control, Leibniz University Hannover, Germany
2Department of Internal Medicine I, Ruhr University Bochum, Germany
3Center for Rare Diseases Ruhr, Ruhr University Bochum, Germany
4Diabetes Centre Bochum-Hattingen, Germany
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-T4) monotherapy or a liothyronine/levothyroxine (L-T3/L-T4) combined therapy is more suitable to treat hypothyroidism. Third, the optimal intake frequency of L-T3/L-T4 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-T3 and L-T4. 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-T3/L-T4 combined therapy is slightly better (in terms of the achieved hormone concentrations) to treat hypothyroidism than the L-T4 monotherapy. In case of a specific genetic variant, namely genotype CC in polymorphism rs2235544 of gene DIO1, the simulation results suggest that the L-T4 monotherapy is better to treat hypothyroidism. In turn, when genotype AA is considered, the L-T3/L-T4 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-T3/L-T4 combined therapy is better in terms of the steady-state hormone concentrations (for a T3 setpoint at the upper limit of the reference range of healthy individuals). Finally, the results suggest that two daily intakes of L-T3 could be the best trade-off between stable hormone concentrations and inconveniences for the patient.
