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A patient-specific treatment model for Graves' hyperthyroidism.
Balamurugan Pandiyan1, Stephen J Merrill2, Flavia Di Bari3
1Department of Mathematics, University of Wisconsin - Whitewater, 800 W. Main Street, Whitewater, 53190, WI, USA. balamurugan.pandiyan@gmail.com.
Theoretical Biology & Medical Modelling
|January 10, 2018
Summary
This study models Graves' disease treatment using Methimazole (MMI). The model simulates patient progression from hyperthyroidism to euthyroidism, aiding in personalized MMI dosing and treatment duration decisions for better outcomes.
Area of Science:
- Endocrinology
- Computational Biology
- Pharmacology
Background:
- Graves' disease is an autoimmune disorder causing hyperthyroidism via thyroid receptor antibodies (TRAb).
- Thyroid stimulating hormone (TSH) mimics TRAb action, stimulating the thyroid hormone receptor (TSHR).
- Methimazole (MMI) is a standard treatment for hyperthyroidism in Graves' disease patients.
Purpose of the Study:
- To develop a mathematical model simulating hyperthyroidism treatment with MMI.
- To predict patient response to MMI therapy and optimize treatment schedules.
- To guide clinical decisions regarding MMI dosage and discontinuation based on physiological parameters.
Main Methods:
- Developed an ordinary differential equation model with four state variables: MMI concentration, free thyroxine (FT4), TRAb concentration, and thyroid gland size.
- Incorporated thirteen parameters to simulate disease progression.
- Validated model predictions against clinical data from four patients.
Main Results:
- Without MMI, a stable hyperthyroid state exists.
- MMI treatment shifts the state from hyperthyroidism towards subclinical hyperthyroidism and then euthyroidism.
- Model simulations accurately reflect patient data progression.
Conclusions:
- The model can describe, test, and predict patient treatment schedules for Graves' disease.
- It facilitates personalized MMI dosing, including loading and maintenance doses.
- The model aids in determining optimal MMI discontinuation timing based on FT4 levels to maintain euthyroidism and prevent relapse.