{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:13:14Z","timestamp":1787026394583,"version":"build-2736575974"},"reference-count":12,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To: (1) update and refine the predictive abilities of original p-THYROSIM, 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 (\n                      <jats:italic>H<\/jats:italic>\n                      ), weights (\n                      <jats:italic>W<\/jats:italic>\n                      ) and sex. Refinements include dependence on\n                      <jats:italic>H<\/jats:italic>\n                      and\n                      <jats:italic>W<\/jats:italic>\n                      separately, rather than composite\n                      <jats:italic>\n                        BMI=W\/H\n                        <jats:sup>2<\/jats:sup>\n                      <\/jats:italic>\n                      . And to: (2) 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Original p-THYROSIM was refined and updated, first by refitting male and female data for establishing blood volume\n                      <jats:italic>\n                        V\n                        <jats:sub>b<\/jats:sub>\n                      <\/jats:italic>\n                      as a function of\n                      <jats:italic>W<\/jats:italic>\n                      s and\n                      <jats:italic>H<\/jats:italic>\n                      s 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 also developed two software packages for simulating the model: (1) a 100-day iOS implementation for the iPhone and iPad using Apple developer tools; and (2) a 1000-day version in Python, with time units converted from hours to days to render it more practical for research use with clinical diseases that evolve over months and years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The iOS app was 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. With the Python version, graphic hormone responses for 240 days of evolving mono- and combination replacement therapies were illustrated for a simulated Hashimoto\u2019s disease patient. With both versions, simulated combination therapy was shown to be more effective in achieving normal range FT4, FT3 and TSH concentrations in plasma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      p-THYROSIM can predictively provide accurate mono- and combination LT4+LT3 replacement hormone therapies for male and female hypothyroid patients, personalized with their\n                      <jats:italic>H<\/jats:italic>\n                      s and\n                      <jats:italic>W<\/jats:italic>\n                      s. Where combination therapy is warranted, our results predict that not much LT3 (typically 5 \u2013 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.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1735282","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T05:15:08Z","timestamp":1767935708000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Personalized p-THYROSIM model for thyroid hormone dynamics, hypothyroidism treatment &amp; implementation in an iOS version for wide distribution"],"prefix":"10.3389","volume":"16","author":[{"suffix":"III","given":"Joseph","family":"DiStefano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Reid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Ghabra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruthi Sathya","family":"Narayanan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fendo.2022.888429","article-title":"Optimized replacement T4 and T4+T3 dosing in male and female hypothyroid patients with different BMIs using a personalized mechanistic model of thyroid hormone regulation dynamics","volume":"13","author":"Cruz-Loya","year":"2022","journal-title":"Front Endocrinol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1093\/ejendo\/lvad172","article-title":"Randomized double-blind placebo-controlled trial on levothyroxine and liothyronine combination therapy in totally thyroidectomized subjects: the LEVOLIO study","volume":"190","author":"Brigante","year":"2024","journal-title":"Eur J Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2009.0349","article-title":"TSH regulation dynamics in central and extreme primary hypothyroidism","volume":"20","author":"Eisenberg","year":"2010","journal-title":"Thyroid"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.56.4.605","article-title":"Prediction of the normal blood volume. 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