Personalized p-THYROSIM model for thyroid hormone dynamics, hypothyroidism treatment & implementation in an iOS version for wide distribution.

Blood volume (Vb) was refit as a function of weight and height separately for males and females, replacing the composite BMI formulation used in original p-THYROSIM.

• Original p-THYROSIM used BMI (W/H²) as a composite measure; refinement instead uses weight (W) and height (H) as separate independent variables.
• Male and female data were refit separately to establish Vb as a function of Ws and Hs of males and females.
• A superfluous parameter was also removed during model refinement.
• FT4 and FT3 output plotting were slightly adjusted to align them with current assay ranges.

An iOS implementation of p-THYROSIM was developed for iPhone and iPad supporting 100-day simulations of thyroid hormone dynamics.

• The iOS app was implemented using Apple developer tools.
• The app supports 100-day simulations of thyroid hormone regulation.
• The app was exercised and tested in several clinical applications including hemi-thyroidectomy and optimal dosing scenarios.
• Simulation results for hemi-thyroidectomy and for mono- and combination hormone replacement therapies were compared using the iOS app.

A Python version of p-THYROSIM was developed supporting 1000-day simulations with time units converted from hours to days.

• Time units were converted from hours to days to render the Python version more practical for research use with clinical diseases that evolve over months and years.
• The Python version supports up to 1000-day simulations.
• Graphic hormone responses for 240 days of evolving mono- and combination replacement therapies were illustrated for a simulated Hashimoto's disease patient using the Python version.

Simulated combination LT4+LT3 therapy was shown to be more effective than monotherapy in achieving normal range FT4, FT3, and TSH concentrations in plasma.

• Both the iOS and Python versions demonstrated that combination therapy better restored euthyroid levels compared to monotherapy.
• Results were demonstrated for both hemi-thyroidectomy scenarios and Hashimoto's disease patient simulations.
• Normal range FT4, FT3, and TSH concentrations were used as the outcome targets for evaluating therapy effectiveness.

Model predictions indicate that only small doses of LT3 (typically 5–7.5 µg) are needed in addition to LT4 to restore euthyroid levels in combination therapy.

• The paper states 'not much LT3 (typically 5 - 7.5 ug) is needed in addition to LT4 to restore euthyroid levels.'
• Larger LT3 doses were described as 'rarely needed.'
• These findings suggest opportunities for further research exploring safe and effective combination therapy with lower T3 doses.
• The authors also suggest research into slow-releasing T3 formulations as a direction supported by these predictions.

The personalized p-THYROSIM model can simulate thyroid hormone dynamics for both male and female hypothyroid patients using individually measured heights and weights as inputs.

• Personalization is based on individual hormone levels, heights (H), weights (W), and sex.
• The model mathematically mimics the thyroid hormone regulation system in humans.
• The model is designed to optimize replacement LT4 and LT4+LT3 dosing for hypothyroid patients.
• Separate parameterization for males and females was implemented in the blood volume calculation.