SimThyr
SimThyr
Ruhr-Universität Bochum



SimThyr is an international academic project that is being actively developed by scientists in several continents.

The first versions of SimThyr (Genesis and Skyrun) have been developed by Johannes W. Dietrich at the Downtown Medical Hospitals of the Ludwig-Maximilian University of Munich between 1994 and 2000. Primary intention was to test hypotheses about dynamic behaviour of thyrotropic feedback control. One of the key results was a theory about pulsatile TSH secretion to emerge from ultrashort feedback control at the anterior pituitary lobe - an assumption that has later been proved independently and with different methods by LJ Brokken, WM Wiersinga and MF Prummel from the University of Amsterdam.

SimThyr 2.0 (Siboto), released in August 2002, was the first easy-to-use version with a mature graphical user interface (GUI) and it was the first version to be disclosed for public. It is still available as a free download for classic Mac OS (Mac OS 6 to 9).

A new version, SimThyr 3.0 (Mirano), has been published in 2011. Beginning with this version, SimThyr supports modern operating systems like Mac OS X, Linux and current Windows versions. This application has received numerous software awards.

SimThyr version 3.1 (Hyperborea) introduced sensitivity analysis, an advanced modelling technique. Beginning with version 3.2 (Meridian) new options for data export and extended functions for sensitivity analysis have been implemented. SimThyr 3.3 (Gaia) introduced two-way sensitivity analysis and enhanced methods to study predicted equilibrium levels.

SimThyr 4.0 (Merlion) is a major re-write that introduced multiple new concepts including null isocline (aka nullcline) plots and compliance to MIRIAM and MIASE guidelines.

The algorithms underlying the simulation and their scientific implications have been released in several publications.



An early version of SimThyr (1.0) on a Macintosh SE running Mac OS 6.0.7 (ca. 2000) -> Screenshot

Contributors

Johannes W. Dietrich: Initiator and main developer

Martin Adler: Technical advise

Matthias Holzer: Technical advise

Phil Hess: Technical advise

Martin R. Fischer: General support

C. Renate Pickardt: Scientific advice (thyroidology)

Ulla Mitzdorf †: Scientific advice (mathematical modelling)

Rudolf Hörmann: Scientific advice (endocrine cybernetics)

John E. Midgley: Scientific advice (endocrine cybernetics)

Henrik Glensbo: Testing




How to Cite SimThyr

SimThyr has been curated by SciCrunch, zenodo and openAIRE. You may cite SimThyr properly as SimThyr, RRID:SCR_014351. Optionally, you might want to link to http://scicrunch.org/browse/resources/SCR_014351. The Digital Object Identifier (DOI) for SimThyr is 10.5281/zenodo.1303822.




References

Dietrich, J. W., A. Tesche, C. R. Pickardt und U. Mitzdorf (2004). "Thyrotropic Feedback Control: Evidence for an Additional Ultrashort Feedback Loop from Fractal Analysis." Cybernetics and Systems 35 (4): 315-31. doi:10.1080/01969720490443354.

Dietrich, J. W. (2000). "Signal Storage in Metabolic Pathways: The ASIA Element." kybernetiknet 1 (3, 2000): 1-9. [Original paper]

Dietrich, J. W., M. R. Fischer, J. Jauch, E. Pantke, R. Gärtner und C. R. Pickardt (1999). "SPINA-THYR: A novel systems theoretic approach to determine the secretion capacity of the thyroid gland." European Journal of Internal Medicine 10 (Suppl. 1) (May 1999): S34.

Dietrich, J. W., U. Mitzdorf, R. Weitkunat und C. R. Pickardt (1997). "The pituitary-thyroid feedback control: stability and oscillations in a new nonlinear model." Journal of Endocrinological Investigation 20 (Suppl. to no. 5): 100.

Dietrich, J. W. (2002). Der Hypophysen-Schilddrüsen-Regelkreis. Entwicklung und klinische Anwendung eines nichtlinearen Modells. Berlin, Logos-Verlag.

Dietrich, J. W., A. Tesche, C. R. Pickardt und U. Mitzdorf (2002). Fractal Properties of the Thyrotropic Feedback Control: Implications of a Nonlinear Model Compared with Empirical Data. In: Cybernetics and Systems 2002. R. Trappl (Hrsg). Vienna, Austrian Society for Cybernetic Studies: 329-34.

Dietrich, J. W. und B. O. Boehm (2006). Equilibrium behaviour of feedback-coupled physiological saturation kinetics. In: Cybernetics and Systems 2006. R. Trappl (Hrsg). Vienna, Austrian Society for Cybernetic Studies. 1: 269-74.

Dietrich, J. W., G. Landgrafe, E. H. Fotiadou (2012). TSH and thyrotropic agonists: Key actors in thyroid homeostasis. Journal of Thyroid Research, vol. 2012, Article ID 351864, 29 pages, 2012. PMID 23365787, doi:10.1155/2012/351864.

Hoermann, R., J. E. M. Midgley, R. Larisch, J. W. Dietrich (2013). Is Pituitary Thyrotropin an Adequate Measure Of Thyroid Hormone-Controlled Homeostasis During Thyroxine Treatment?. European Journal of Endocrinology 168(2):271-80. PMID 23184912, doi:10.1530/EJE-12-0819.

Midgley, J. E. M., R. Hoermann, R. Larisch, J. W. Dietrich (2013). Physiological states and functional relation between thyrotropin and free thyroxine in thyroid health and disease: in vivo and in silico data suggest a hierarchical model. Journal of Clinical Pathology 66(4):335-42. PMID 23423518, doi:10.1136/jclinpath-2012-201213

Hoermann R, Midgley JE, Larisch R, Dietrich JW (2015). Integration of Peripheral and Glandular Regulation of Triiodothyronine Production by Thyrotropin in Untreated and Thyroxine-Treated Subjects. Hormone and Metabolic Research, PMID: 25750078 doi: 10.1055/s-0034-1398616.

Dietrich JW, Landgrafe-Mende G, Wiora E, Chatzitomaris A, Klein HH., Midgley JE, Hoermann R  (2016). Calculated parameters of thyroid homeostasis: Emerging tools for differential diagnosis and clinical research. Frontiers in Endocrinology. 2016; 7:00057. PMID 27375554. doi: 10.3389/fendo.2016.00057.

Chatzitomaris A, Hoermann R, Midley JE, Hering S, Urban A, Dietrich B, Abood A, Klein HH, Dietrich JW (2017). Thyroid Allostasis – Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress and Developmental Programming. Frontiers in Endocrinology. 2017; 8:00163. PMID 28775711. doi: 10.3389/fendo.2017.00163

Hoermann R, Midgley JEM, Larisch R, Dietrich JW (2018). The role of functional thyroid capacity in pituitary thyroid feedback regulation. Eur J Clin Invest. 2018 Oct;48(10):e13003. doi: 10.1111/eci.13003. PMID: 30022470.



Other Citations

Lupínek, J. (2012). Freeware simulační a vizualizační nástroje pro GNU/Linux. Západočeská univerzita v Plzni. Fakulta elektrotechnická, Katedra elektromechaniky a výkonové elektroniky. PDF version.

Han, Simon Xian He (2013). THYROSIM: A Web Application for Human Thyroid System Regulation Education and Research. UCLA Electronic Theses and Dissertations.

Arslan, M. Oguz (2014). Özgür ve Açık Kaynak Yazılımın Ekonomik Faydaları: Saglık Sektörü Için Bir Degerlendirme [Economic Benefits of Free and Open Source Software: An Evaluation for Health Sector.]

Hoermann R, Midgley JEM, Larisch R, Dietrich JWC (2017). Advances in applied homeostatic modelling of the relationship between thyrotropin and free thyroxine. PLoS One. 2017 Nov 20;12(11):e0187232. doi 10.1371/journal.pone.0187232. PMID 29155897.

Ramos A, Chaves R, Favero E. (2019). Simulação baseada em Dinâmica de Sistemas para o ensino da fisiologia do eixo Hipotálamo-hipófise-tireoide no contexto da graduação em medicina. Simpósio Brasileiro de Informática na Educação - SBIE. doi 10.5753/cbie.sbie.2019.962.




Press Coverage

Dan Gezelter: SimThyr – simulation software for pituitary thyroid feedback, OpenScience, May 2013.

BergmannsheilReport 03/2014: "Ausgezeichnetes E-Learning-Angebot", September 2014: 4.

Life Science Network: Systems level in-silico analysis helps to identify new mechanisms of thyroid homeostasis. April 2015.

BergmannsheilReport 03/2015: "Neue Therapie bei Schilddrüsenunterfunktion?", September 2015: 7.






Links




SimThyr project entry
                    at sourceforge.net