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Research Article: Stability-aware LSTM–MPC framework for personalized levothyroxine dosing in Hashimoto’s thyroiditis

Date Published: 2026-08-13

Abstract:
Hypothyroidism, most commonly caused by Hashimoto’s thyroiditis, is characterized by insufficient production of thyroid hormones and is typically treated with oral levothyroxine (LT4). However, determining patient-specific LT4 dosage remains challenging due to significant inter-individual variability and the need for repeated clinical adjustments. In this study, a stability-aware, data-driven dosing framework is developed for personalized LT4 therapy. The proposed approach combines a Long Short-Term Memory (LSTM) neural network for predicting free thyroxine (FT4) concentrations with a model predictive control (MPC) strategy for dose optimization. To ensure safe and reliable operation, Input-to-State Stability (ISS) conditions are incorporated within the control framework, ensuring boundedness of the system states and stability of the closed-loop system. The method is evaluated using simulated patients generated with Thyrosim, a validated mathematical simulator of thyroid hormone regulation, under varying biological parameters. Simulation results demonstrate that the proposed framework regulates FT4 concentrations toward patient-specific euthyroid levels during the initial phase of treatment and maintains stable hormone levels throughout the simulation period. Furthermore, consistent performance across a heterogeneous population of simulated patients highlights the robustness of the approach. These findings suggest that the proposed ISS-LSTM-MPC framework provides a promising foundation for automated, personalized LT4 dosing and represents a step toward clinically applicable decision-support systems for thyroid hormone therapy.

Introduction:
Hypothyroidism is a common endocrine disorder characterized by insufficient production of thyroid hormones, primarily thyroxine (T4) and triiodothyronine (T3). A gender-based association highlighted in indicates that hypothyroidism is more prevalent in females than in males, see e.g., Meng and et al ( 1 ). The condition affects approximately 10% of the general population, with nearly half of the affected individuals remaining undiagnosed. If left untreated, hypothyroidism may lead to fatigue, weight gain,…

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