title: THYROSIM App for Education and Research Predicts Potential Health Risks of Over-the-Counter Thyroid Supplements.
abstract: BACKGROUND
  Computer simulation tools for education and research are making increasingly effective use of the Internet and personal devices. To facilitate these activities in endocrinology and metabolism, a mechanistically based simulator of human thyroid hormone and thyrotropin (TSH) regulation dynamics was developed and further validated, and it was implemented as a facile and freely accessible web-based and personal device application: the THYROSIM app. This study elucidates and demonstrates its utility in a research context by exploring key physiological effects of over-the-counter thyroid supplements.
  
  
  METHODS
  THYROSIM has a simple and intuitive user interface for teaching and conducting simulated "what-if" experiments. User-selectable "experimental" test-input dosages (oral, intravenous pulses, intravenous infusions) are represented by animated graphical icons integrated with a cartoon of the hypothalamic-pituitary-thyroid axis. Simulations of familiar triiodothyronine (T3), thyroxine (T4), and TSH temporal dynamic responses to these exogenous stimuli are reported graphically, along with normal ranges on the same single interface page; and multiple sets of simulated experimental results are superimposable to facilitate comparative analyses.
  
  
  CONCLUSIONS
  This study shows that THYROSIM accurately reproduces a wide range of published clinical study data reporting hormonal kinetic responses to large and small oral hormone challenges. Simulation examples of partial thyroidectomies and malabsorption illustrate typical usage by optionally changing thyroid gland secretion and/or gut absorption rates--expressed as percentages of normal--as well as additions of oral hormone dosing, all directly on the interface, and visualizing the kinetic responses to these challenges. Classroom and patient education usage--with public health implications--is illustrated by predictive simulated responses to nonprescription thyroid health supplements analyzed previously for T3 and T4 content. Notably, it was found that T3 in supplements has potentially more serious pathophysiological effects than does T4--concomitant with low-normal TSH levels. Some preparations contain enough T3 to generate thyrotoxic conditions, with supernormal serum T3-spiking and subnormal serum T4 and TSH levels and, in some cases, with normal or low-normal range TSH levels due to thyroidal axis negative feedback. These results suggest that appropriate regulation of these products is needed.
authors.affiliation: 1 Biocybernetics Laboratory, Departments of Computer Science and Medicine, UCLA , Los Angeles, California.
authors.forename: Simon X
authors.initials: SX
authors.lastname: Han
authors.affiliation: 2 Departments of Epidemiology and Mathematics, School of Public Health, University of Michigan , Ann Arbor, Michigan.
authors.forename: Marisa
authors.initials: M
authors.lastname: Eisenberg
authors.affiliation: 3 Brigham and Women's Hospital/Harvard Medical School , Department of Medicine, Boston, Massachusetts.
authors.forename: P Reed
authors.initials: PR
authors.lastname: Larsen
authors.affiliation: 1 Biocybernetics Laboratory, Departments of Computer Science and Medicine, UCLA , Los Angeles, California.
authors.forename: Joseph
authors.initials: J
authors.lastname: DiStefano
mesh_terms: D000284:Administration, Oral; D003198:Computer Simulation; D034201:Computers, Handheld; D004704:Endocrinology / Q000193:education / Q000379:methods; D006801:Humans; D020407:Internet; D007700:Kinetics; D063731:Mobile Applications; D004366:Nonprescription Drugs; D013959:Thyroid Diseases / Q000188:drug therapy*; D013961:Thyroid Gland / Q000187:drug effects*; D013963:Thyroid Hormones / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism; D014584:User-Computer Interface
chemical_list: D004366:Nonprescription Drugs; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine