ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Thyroid Endocrinology
This article is part of the Research TopicMechanistic, Machine Learning and Hybrid Models of the 'Other' Endocrine Regulatory Systems in Health and Disease: Volume IIView all 5 articles
Personalized p-THYROSIM Model for Thyroid Hormone Dynamics, Hypothyroidism Treatment & Implementation in an iOS Version for Wide Distribution
Provisionally accepted
- University of California, Los Angeles, Los Angeles, United States
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Objective To update and refine the predictive abilities of original p-THYROSIM (1), a uniquely personalized simulation tool that mathematically mimics the thyroid hormone regulation system in humans, to optimize replacement LT4 and LT4+LT3 dosing for hypothyroid patients, based on individual hormone levels, heights (H), weights (W) and sex. To present a new and user-friendly software tool, an iOS p-THYROSIM app for the iPhone and iPad, to accomplish these goals, as well as a Python version for longer term disease progression simulations. Methods Original p-THYROSIM (1) was refined and updated, first by refitting male and female data for establishing blood volume Vb as a function of Ws and Hs of males and females separately. A superfluous parameter was also removed and FT4 and FT3 output plotting were slightly adjusted to align them with current assay ranges. We developed two software packages for simulating the model: (1) a 100-day iOS implementation of the model for the iPhone and iPad using Apple developer tools (illustrated it in several clinical examples); and (2), to render it more practical for research use with clinical diseases that evolve over months and years, we converted time units in the iOS implementation from hours to days and developed a 1000 day version in Python. Results The iOS app has been implemented, exercised and tested in several clinical applications. Most notably, simulation results are shown and compared for hemi-thyroidectomy and for optimal dosing for mono-and combination hormone replacement therapies. In the latter, combination therapy is shown to be more effective in achieving normal range FT4 and FT4 concentrations in plasma. Conclusions p-THYROSIM can provide accurate mono-and combination LT4+LT3 replacement hormone therapies for male and female hypothyroid patients, personalized with their Hs and Ws. Where combination therapy is warranted, our results predict that not much LT3 (typically 5 – 7.5 ug) is needed in addition to LT4 to restore euthyroid levels, with larger LT3 doses rarely needed, suggesting opportunities for further research exploring safe and effective combination therapy with lower T3 doses and slow-releasing T3 formulations.
Keywords: Math model, simulation model, residual thyroid function, Optimal dosing, personalized medicine, Monotherapy, combination hormone replacement therapy
Received: 29 Oct 2025; Accepted: 02 Dec 2025.
Copyright: © 2025 DiStefano III, Reid, Ghabra, Chen and Narayanan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Joseph DiStefano III
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