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{{Infobox software
{{Infobox software
| name = SimThyr
| name = <!-- automatically populated from Wikidata -->
| logo = File:SimThyr new 512x512x32.png
| logo = File:SimThyr new 512x512x32.png
| logo alt = SimThyr icon
| logo alt = SimThyr icon
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| author = Johannes W. Dietrich, [[Ulla Mitzdorf]], [[Renate Pickardt]], Rudolf Hoermann, John E. M. Midgley
| author = Johannes W. Dietrich, [[Ulla Mitzdorf]], [[Renate Pickardt]], Rudolf Hoermann, John E. M. Midgley
| developer = [[Ruhr University Bochum]]
| developer = [[Ruhr University Bochum]]
| released = 2002
| released = {{start date and age|df=yes|paren=yes|2002}}
| latest release version = 4.0.3
| latest release version = 4.0.6
| latest release date = {{Start date and age|2020|08|31}}
| latest release date = {{Start date and age|2022|04|23}}
| operating system = [[macOS]], [[Windows]] and [[Linux]]
| operating system = [[macOS]], [[Windows]] and [[Linux]]
| platform = [[PowerPC]], [[IA-32]], [[x86-64]] and [[ARM processor|ARM]],<br/>[[Motorola 68000 series|m68k]] (legacy versions only)
| platform = [[PowerPC]], [[IA-32]], [[x86-64]] and [[ARM processor|ARM]],<br/>[[Motorola 68000 series|m68k]] (legacy versions only)
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| repo = <!-- automatically populated from Wikidata -->
| repo = <!-- automatically populated from Wikidata -->
| language = British English, German (SimThyr 2.0 or older only)
| language = British English, German (SimThyr 2.0 or older only)
| qid = Q59421094
| programming language = [[Pascal (programming language)|Pascal]] and [[Object Pascal]]
| programming language = [[Pascal (programming language)|Pascal]] and [[Object Pascal]]
| engines =
| engines =
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}}
}}


'''SimThyr''' is a free continuous [[Dynamic simulation|dynamic]] [[Computer simulation|simulation]] [[Program (computer science)|program]] for the [[Hypothalamic–pituitary–thyroid axis|pituitary-thyroid feedback control]] system.<ref name = "Dietrich_2012">{{cite journal |last1=Dietrich |first1=JW |last2=Landgrafe |first2=G |last3=Fotiadou |first3=EH |title=TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis. |journal=Journal of Thyroid Research |date=2012 |volume=2012 |pages=351864 |doi=10.1155/2012/351864 |pmid=23365787|pmc=3544290 }}</ref> The [[Open-source software|open-source]] program is based on a [[Nonlinear system|nonlinear model]] of thyroid homeostasis.<ref>{{cite journal |last1=Hoermann |first1=R |last2=Midgley |first2=JE |last3=Larisch |first3=R |last4=Dietrich |first4=JW |title=Homeostatic Control of the Thyroid-Pituitary Axis: Perspectives for Diagnosis and Treatment. |journal=Frontiers in Endocrinology |date=2015 |volume=6 |pages=177 |doi=10.3389/fendo.2015.00177 |pmid=26635726 |pmc=4653296 }}</ref><ref name="Berberich_2018">{{cite journal |last1=Berberich |first1=Julian |title=Mathematical Modeling of the Pituitary-Thyroid Feedback Loop: Matlab/Simulink Files for Simulation and Sensitivity Analysis |date=13 September 2018 |doi=10.5281/zenodo.1415331 }}</ref><ref name="Dietrich_2002">{{cite book |last1=Dietrich |first1=Johannes W. |title=Der Hypophysen-Schilddrüsen-Regelkreis : Entwicklung und klinische Anwendung eines nichtlinearen Modells |date=2002 |publisher=Logos-Verlag |location=Berlin |isbn=978-3897228504}}</ref> In addition to simulations in the [[Time-domain state space representation|time domain]] the software supports various methods of [[sensitivity analysis]]. Its simulation engine is [[multi-threaded]] and supports multiple [[Central processing unit|processor cores]]. SimThyr provides a [[GUI]], which allows for [[Visualization (graphics)|visualising]] [[time series]], modifying constant structure parameters of the [[feedback loop]] (e.g. for simulation of certain diseases), storing parameter sets as [[XML]] files (referred to as "scenarios" in the software) and exporting results of simulations in various formats that are suitable for statistical software. SimThyr is intended for both [[Higher education|educational]] purposes and [[In silico|in-silico]] research.<ref name="Dietrich_2002"/><ref>{{cite book |last1=Dietrich |first1=Johannes W. |last2=Midgley |first2=John E. M. |last3=Hoermann |first3=Rudolf |title=Homeostasis and Allostasis of Thyroid Function |date=2018 |publisher=Frontiers Media SA |location=Lausanne |isbn=9782889455706}}</ref>
'''SimThyr''' is a free continuous [[Dynamic simulation|dynamic]] [[Computer simulation|simulation]] [[Program (computer science)|program]] for the [[Hypothalamic–pituitary–thyroid axis|pituitary-thyroid feedback control]] system.<ref name = "Dietrich_2012">{{cite journal |last1=Dietrich |first1=JW |last2=Landgrafe |first2=G |last3=Fotiadou |first3=EH |title=TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis. |journal=Journal of Thyroid Research |date=2012 |volume=2012 |pages=351864 |doi=10.1155/2012/351864 |pmid=23365787|pmc=3544290 |doi-access=free }}</ref> The [[Open-source software|open-source]] program is based on a [[Nonlinear system|nonlinear model]] of thyroid homeostasis.<ref>{{cite journal |last1=Hoermann |first1=R |last2=Midgley |first2=JE |last3=Larisch |first3=R |last4=Dietrich |first4=JW |title=Homeostatic Control of the Thyroid-Pituitary Axis: Perspectives for Diagnosis and Treatment. |journal=Frontiers in Endocrinology |date=2015 |volume=6 |pages=177 |doi=10.3389/fendo.2015.00177 |pmid=26635726 |pmc=4653296 |doi-access=free }}</ref><ref name="Berberich_2018">{{cite journal |last1=Berberich |first1=Julian |title=Mathematical Modeling of the Pituitary-Thyroid Feedback Loop: Matlab/Simulink Files for Simulation and Sensitivity Analysis |date=13 September 2018 |doi=10.5281/zenodo.1415331 }}</ref><ref name="Dietrich_2002">{{cite book |last1=Dietrich |first1=Johannes W. |title=Der Hypophysen-Schilddrüsen-Regelkreis : Entwicklung und klinische Anwendung eines nichtlinearen Modells |date=2002 |publisher=Logos-Verlag |location=Berlin |isbn=978-3897228504}}</ref> In addition to simulations in the [[Time-domain state space representation|time domain]] the software supports various methods of [[sensitivity analysis]]. Its simulation engine is [[multi-threaded]] and supports multiple [[Central processing unit|processor cores]]. SimThyr provides a [[GUI]], which allows for [[Visualization (graphics)|visualising]] [[time series]], modifying constant structure parameters of the [[feedback loop]] (e.g. for simulation of certain diseases), storing parameter sets as [[XML]] files (referred to as "scenarios" in the software) and exporting results of simulations in various formats that are suitable for statistical software. SimThyr is intended for both [[Higher education|educational]] purposes and [[In silico|in-silico]] research.<ref name="Dietrich_2002"/><ref>{{cite book |last1=Dietrich |first1=Johannes W. |last2=Midgley |first2=John E. M. |last3=Hoermann |first3=Rudolf |title=Homeostasis and Allostasis of Thyroid Function |date=2018 |publisher=Frontiers Media SA |location=Lausanne |isbn=9782889455706}}</ref>


== Mathematical model ==
== Mathematical model ==
The underlying model of thyroid homeostasis is based on fundamental biochemical, physiological and pharmacological principles, e.g. [[Michaelis-Menten kinetics]], [[non-competitive inhibition]] and empirically justified [[Pharmacokinetics simulation|kinetic]] parameters.<ref name = "Dietrich_2012"/> The model has been validated in healthy controls and in cohorts of patients with hypothyroidism and thyrotoxicosis.<ref>{{cite journal |last1=Hoermann |first1=R |last2=Pekker |first2=MJ |last3=Midgley |first3=JEM |last4=Larisch |first4=R |last5=Dietrich |first5=JW |title=Triiodothyronine secretion in early thyroid failure: The adaptive response of central feedforward control. |journal=European Journal of Clinical Investigation |date=February 2020 |volume=50 |issue=2 |pages=e13192 |doi=10.1111/eci.13192 |pmid=31815292|s2cid=208956920 }}</ref>
The underlying model of thyroid homeostasis is based on fundamental biochemical, physiological and pharmacological principles, e.g. [[Michaelis-Menten kinetics]], [[non-competitive inhibition]] and empirically justified [[Pharmacokinetics simulation|kinetic]] parameters.<ref name = "Dietrich_2012"/> The model has been validated in healthy controls and in cohorts of patients with [[hypothyroidism]] and [[thyrotoxicosis]].<ref>{{cite journal |last1=Hoermann |first1=R |last2=Pekker |first2=MJ |last3=Midgley |first3=JEM |last4=Larisch |first4=R |last5=Dietrich |first5=JW |title=Triiodothyronine secretion in early thyroid failure: The adaptive response of central feedforward control. |journal=European Journal of Clinical Investigation |date=February 2020 |volume=50 |issue=2 |pages=e13192 |doi=10.1111/eci.13192 |pmid=31815292|s2cid=208956920 }}</ref>


== Scientific uses ==
== Scientific uses ==
[[File:SimThyr in computer resource centre.jpg|thumb|right|SimThyr used for educational purposes in a computer resource centre]]
[[File:SimThyr in computer resource centre.jpg|thumb|right|SimThyr used for educational purposes in a computer resource centre]]
Multiple studies have employed SimThyr for in silico research on the control of [[thyroid]] function.<ref>{{cite journal |last1=Ramos |first1=André |last2=Chaves |first2=Rafael |last3=Favero |first3=Elói |title=Simulação baseada em Dinâmica de Sistemas para o ensino da fisiologia do eixo Hipotálamo-hipófise-tireoide no contexto da graduação em medicina |journal=Brazilian Symposium on Computers in Education (Simpósio Brasileiro de Informática Na Educação - SBIE) |date=11 November 2019 |volume=30 |issue=1 |pages=962 |doi=10.5753/cbie.sbie.2019.962 |language=pt |issn=2316-6533}}</ref><ref>{{cite journal |last1=Ghosh |first1=Devleena |last2=Mandal |first2=Chittaranjan |title=Clustering Based Parameter Estimation of Thyroid Hormone Pathway |journal=IEEE/ACM Transactions on Computational Biology and Bioinformatics |date=2020 |volume=PP |pages=1 |doi=10.1109/TCBB.2020.2995589|pmid=32750849 }}</ref>
Multiple studies have employed SimThyr for in silico research on the control of [[thyroid]] function.<ref>{{cite journal |last1=Ramos |first1=André |last2=Chaves |first2=Rafael |last3=Favero |first3=Elói |title=Simulação baseada em Dinâmica de Sistemas para o ensino da fisiologia do eixo Hipotálamo-hipófise-tireoide no contexto da graduação em medicina |journal=Brazilian Symposium on Computers in Education (Simpósio Brasileiro de Informática Na Educação - SBIE) |date=11 November 2019 |volume=30 |issue=1 |pages=962 |doi=10.5753/cbie.sbie.2019.962 |s2cid=213401607 |language=pt |issn=2316-6533|doi-access=free }}</ref><ref>{{cite journal |last1=Ghosh |first1=Devleena |last2=Mandal |first2=Chittaranjan |title=Clustering Based Parameter Estimation of Thyroid Hormone Pathway |journal=IEEE/ACM Transactions on Computational Biology and Bioinformatics |date=2020 |volume=PP |issue=1 |pages=343–354 |doi=10.1109/TCBB.2020.2995589|pmid=32750849 |s2cid=219479222 }}</ref>


The original version was developed to check hypotheses about the generation of [[Pulsatile secretion|pulsatile]] [[Thyrotropin|TSH]] release.<ref>{{cite journal |last1=DIETRICH |first1=J. W. |last2=TESCHE |first2=A. |last3=PICKARDT |first3=C. R. |last4=MITZDORF |first4=U. |title=Thyrotropic Feedback Control: Evidence for an Additional Ultrashort Feedback Loop from Fractal Analysis |journal=Cybernetics and Systems |date=2004 |volume=35 |issue=4 |pages=315–331 |doi=10.1080/01969720490443354|s2cid=13421388 }}</ref> Later and expanded versions of the software were used to develop the hypothesis of the [[TSH-T3 shunt]] in the hypothalamus-pituitary-thyroid axis,<ref>{{cite journal |last1=Hoermann |first1=R |last2=Midgley |first2=JE |last3=Larisch |first3=R |last4=Dietrich |first4=JW |title=Integration of Peripheral and Glandular Regulation of Triiodothyronine Production by Thyrotropin in Untreated and Thyroxine-Treated Subjects |journal=Horm Metab Res |date=2015 |volume=47 |issue=9 |pages=674–80 |doi=10.1055/s-0034-1398616 |pmid=25750078|url=https://zenodo.org/record/918309 }}</ref> to assess the validity of calculated parameters of thyroid homeostasis (including [[Thyroid's secretory capacity|SPINA-GT]] and [[Sum activity of peripheral deiodinases|SPINA-GD]])<ref>{{cite journal |last1=Dietrich |first1=JW |last2=Landgrafe-Mende |first2=G |last3=Wiora |first3=E |last4=Chatzitomaris |first4=A |last5=Klein |first5=HH |last6=Midgley |first6=JE |last7=Hoermann |first7=R |title=Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research. |journal=Frontiers in Endocrinology |date=2016 |volume=7 |pages=57 |doi=10.3389/fendo.2016.00057 |pmid=27375554 |pmc=4899439 }}</ref><ref>{{cite journal |last1=Hoermann |first1=Rudolf |last2=Midgley |first2=John E. M. |last3=Larisch |first3=Rolf |last4=Dietrich |first4=Johannes W. |title=The role of functional thyroid capacity in pituitary thyroid feedback regulation |journal=European Journal of Clinical Investigation |date=October 2018 |volume=48 |issue=10 |pages=e13003 |doi=10.1111/eci.13003 |pmid=30022470|s2cid=51698223 }}</ref> and to study [[Allostasis|allostatic]] mechanisms leading to [[non-thyroidal illness syndrome]].<ref>{{cite journal |last1=Hoermann |first1=R |last2=Midgley |first2=JE |last3=Larisch |first3=R |last4=Dietrich |first4=JW |title=Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment? |journal=European Journal of Endocrinology |date=February 2013 |volume=168 |issue=2 |pages=271–80 |doi=10.1530/EJE-12-0819 |pmid=23184912}}</ref><ref>{{cite journal |last1=Chatzitomaris |first1=A |last2=Hoermann |first2=R |last3=Midgley |first3=JE |last4=Hering |first4=S |last5=Urban |first5=A |last6=Dietrich |first6=B |last7=Abood |first7=A |last8=Klein |first8=HH |last9=Dietrich |first9=JW |title=Thyroid Allostasis-Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming. |journal=Frontiers in Endocrinology |date=2017 |volume=8 |pages=163 |doi=10.3389/fendo.2017.00163 |pmid=28775711|pmc=5517413 }}</ref>
The original version was developed to check hypotheses about the generation of [[Pulsatile secretion|pulsatile]] [[Thyrotropin|TSH]] release.<ref>{{cite journal |last1=DIETRICH |first1=J. W. |last2=TESCHE |first2=A. |last3=PICKARDT |first3=C. R. |last4=MITZDORF |first4=U. |title=Thyrotropic Feedback Control: Evidence for an Additional Ultrashort Feedback Loop from Fractal Analysis |journal=Cybernetics and Systems |date=2004 |volume=35 |issue=4 |pages=315–331 |doi=10.1080/01969720490443354|s2cid=13421388 }}</ref> Later and expanded versions of the software were used to develop the hypothesis of the [[TSH-T3 shunt]] in the hypothalamus-pituitary-thyroid axis,<ref>{{cite journal |last1=Hoermann |first1=R |last2=Midgley |first2=JE |last3=Larisch |first3=R |last4=Dietrich |first4=JW |title=Integration of Peripheral and Glandular Regulation of Triiodothyronine Production by Thyrotropin in Untreated and Thyroxine-Treated Subjects |journal=Horm Metab Res |date=2015 |volume=47 |issue=9 |pages=674–80 |doi=10.1055/s-0034-1398616 |pmid=25750078|s2cid=9824656 |url=https://zenodo.org/record/918309 }}</ref> to assess the validity of calculated parameters of thyroid homeostasis (including [[Thyroid's secretory capacity|SPINA-GT]] and [[Sum activity of peripheral deiodinases|SPINA-GD]])<ref>{{cite journal |last1=Dietrich |first1=JW |last2=Landgrafe-Mende |first2=G |last3=Wiora |first3=E |last4=Chatzitomaris |first4=A |last5=Klein |first5=HH |last6=Midgley |first6=JE |last7=Hoermann |first7=R |title=Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research. |journal=Frontiers in Endocrinology |date=2016 |volume=7 |pages=57 |doi=10.3389/fendo.2016.00057 |pmid=27375554 |pmc=4899439 |doi-access=free }}</ref><ref>{{cite journal |last1=Hoermann |first1=Rudolf |last2=Midgley |first2=John E. M. |last3=Larisch |first3=Rolf |last4=Dietrich |first4=Johannes W. |title=The role of functional thyroid capacity in pituitary thyroid feedback regulation |journal=European Journal of Clinical Investigation |date=October 2018 |volume=48 |issue=10 |pages=e13003 |doi=10.1111/eci.13003 |pmid=30022470|s2cid=51698223 }}</ref> and to study [[Allostasis|allostatic]] mechanisms leading to [[non-thyroidal illness syndrome]].<ref>{{cite journal |last1=Hoermann |first1=R |last2=Midgley |first2=JE |last3=Larisch |first3=R |last4=Dietrich |first4=JW |title=Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment? |journal=European Journal of Endocrinology |date=February 2013 |volume=168 |issue=2 |pages=271–80 |doi=10.1530/EJE-12-0819 |pmid=23184912|s2cid=34158774 |doi-access=free }}</ref><ref>{{cite journal |last1=Chatzitomaris |first1=A |last2=Hoermann |first2=R |last3=Midgley |first3=JE |last4=Hering |first4=S |last5=Urban |first5=A |last6=Dietrich |first6=B |last7=Abood |first7=A |last8=Klein |first8=HH |last9=Dietrich |first9=JW |title=Thyroid Allostasis-Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming. |journal=Frontiers in Endocrinology |date=2017 |volume=8 |pages=163 |doi=10.3389/fendo.2017.00163 |pmid=28775711|pmc=5517413 |doi-access=free }}</ref>


SimThyr was also used to show that the release rate of thyrotropin is controlled by multiple factors other than [[Thyroxine|T4]] and that the relation between [[FT4|free T4]] and TSH may be different in [[euthyroid]]ism, [[hypothyroidism]] and [[thyrotoxicosis]].<ref>{{cite journal |last1=Midgley |first1=JE |last2=Hoermann |first2=R |last3=Larisch |first3=R |last4=Dietrich |first4=JW |title=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=Journal of Clinical Pathology |date=April 2013 |volume=66 |issue=4 |pages=335–42 |doi=10.1136/jclinpath-2012-201213 |pmid=23423518 |s2cid=46291947 |url=https://jcp.bmj.com/content/66/4/335.long |accessdate=4 December 2018}}</ref>
SimThyr was also used to show that the release rate of thyrotropin is controlled by multiple factors other than [[Thyroxine|T4]] and that the relation between [[FT4|free T4]] and TSH may be different in [[euthyroid]]ism, [[hypothyroidism]] and [[thyrotoxicosis]].<ref>{{cite journal |last1=Midgley |first1=JE |last2=Hoermann |first2=R |last3=Larisch |first3=R |last4=Dietrich |first4=JW |title=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=Journal of Clinical Pathology |date=April 2013 |volume=66 |issue=4 |pages=335–42 |doi=10.1136/jclinpath-2012-201213 |pmid=23423518 |s2cid=46291947 |url=https://jcp.bmj.com/content/66/4/335.long |accessdate=4 December 2018}}</ref>
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== Public perception, reception and discussion of the software ==
== Public perception, reception and discussion of the software ==


SimThyr is [[Free software|free]] and [[open-source]] software. This ensures the [[sourcecode]] to be available, which facilitates scientific discussion and reviewing of the underlying model.<ref>{{cite web |last1=Gezelter |first1=Dan |title=SimThyr – simulation software for pituitary thyroid feedback {{!}} The OpenScience Project |url=http://openscience.org/simthyr-simulation-software-for-pituitary-thyroid-feedback/ |website=The OpenScience Project |accessdate=6 February 2019 |archive-url=https://web.archive.org/web/20190404101222/http://openscience.org/simthyr-simulation-software-for-pituitary-thyroid-feedback/ |archive-date=4 April 2019}}</ref><ref>{{cite web |last1=Glensbo |first1=Henrik |title=Fokus i 2020 - stofskiftesygdom.dk |url=https://www.stofskiftesygdom.dk/fokus-i-2020/ |website=www.stofskiftesygdom.dk |publisher=Stofskiftesygdom |accessdate=2 April 2020}}</ref> Additionally, the fact that it is freely available may result in economical benefits.<ref>{{cite book |last1=Lupínek |first1=Jiří |title=Freeware simulační a vizualizační nástroje pro GNU/Linux |date=2012 |publisher=Západočeská univerzita v Plzni |hdl=11025/5282 |language=cs}}</ref><ref>{{cite journal |last1=Arslan |first1=M. Oguz |title=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.] |journal=Hacettepe Sağlık İdaresi Dergisi |date=2014 |volume=17 |pages=119–31 |url=https://www.researchgate.net/publication/274947660}}</ref>
SimThyr is [[Free software|free]] and [[open-source]] software. This ensures the [[source code]] to be available, which facilitates scientific discussion and reviewing of the underlying model.<ref>{{cite web |last1=Gezelter |first1=Dan |title=SimThyr – simulation software for pituitary thyroid feedback {{!}} The OpenScience Project |url=http://openscience.org/simthyr-simulation-software-for-pituitary-thyroid-feedback/ |website=The OpenScience Project |accessdate=6 February 2019 |archive-url=https://web.archive.org/web/20190404101222/http://openscience.org/simthyr-simulation-software-for-pituitary-thyroid-feedback/ |archive-date=4 April 2019}}</ref><ref>{{cite web |last1=Glensbo |first1=Henrik |title=Fokus i 2020 - stofskiftesygdom.dk |url=https://www.stofskiftesygdom.dk/fokus-i-2020/ |website=www.stofskiftesygdom.dk |publisher=Stofskiftesygdom |accessdate=2 April 2020}}</ref> Additionally, the fact that it is freely available may result in economical benefits.<ref>{{cite book |last1=Lupínek |first1=Jiří |title=Freeware simulační a vizualizační nástroje pro GNU/Linux |date=2012 |publisher=Západočeská univerzita v Plzni |hdl=11025/5282 |language=cs}}</ref><ref>{{cite journal |last1=Arslan |first1=M. Oguz |title=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.] |journal=Hacettepe Sağlık İdaresi Dergisi |date=2014 |volume=17 |pages=119–31 |url=https://www.researchgate.net/publication/274947660}}</ref>


The software provides an editor that enables users to modify most structure parameters of the information processing structure.<ref>{{cite journal |last1=Dietrich |first1=J. W. |title=SimThyr 4.0 Handbook and Reference |date=2017 |publisher=figshare |doi=10.6084/m9.figshare.4902098}}</ref> This functionality fosters simulation of several functional diseases of the thyroid and the pituitary gland. Parameter sets may be stored as MIRIAM- and [[Minimum information about a simulation experiment|MIASE]]-compliant XML files.
The software provides an editor that enables users to modify most structure parameters of the information processing structure.<ref>{{cite |last1=Dietrich |first1=J. W. |title=SimThyr 4.0 Handbook and Reference |date=2017 |publisher=figshare |doi=10.6084/m9.figshare.4902098}}</ref> This functionality fosters simulation of several functional diseases of the thyroid and the pituitary gland. Parameter sets may be stored as MIRIAM- and [[Minimum information about a simulation experiment|MIASE]]-compliant XML files.


On the other hand, the complexity of the user interface and the lack of the ability to model treatment effects have been criticized.<ref>{{cite book |last1=Han |first1=Simon Xian He |title=THYROSIM: A Web Application for Human Thyroid System Regulation Education and Research |date=2013 |publisher=UCLA |location=Los Angeles |url=https://escholarship.org/uc/item/59f4r28p |language=en}}</ref>
On the other hand, the complexity of the user interface and the lack of the ability to model treatment effects have been criticized.<ref>{{cite thesis |last1=Han |first1=Simon Xian He |title=THYROSIM: A Web Application for Human Thyroid System Regulation Education and Research |date=2013 |publisher=UCLA |location=Los Angeles |url=https://escholarship.org/uc/item/59f4r28p |language=en}}</ref>


== See also ==
== See also ==
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== External links ==
== External links ==
{{Library resources box|by=no|onlinebooks=no|about=yes|wikititle=SimThyr}}

* {{Official website|http://simthyr.sourceforge.net}} of the SimThyr project
* {{Official website|http://simthyr.sourceforge.net}} of the SimThyr project
* [https://doi.org/10.5281/zenodo.1303822 Curated information at Zenodo]
* [https://doi.org/10.5281/zenodo.1303822 Curated information at Zenodo]
* [http://scicrunch.org/browse/resources/SCR_014351 Curated information at SciCrunch]
* [http://scicrunch.org/browse/resources/SCR_014351 Curated information at SciCrunch]

{{Authority control}}


[[Category:Free science software]]
[[Category:Free science software]]
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[[Category:Free software programmed in Pascal]]
[[Category:Free software programmed in Pascal]]
[[Category:Scientific simulation software]]
[[Category:Scientific simulation software]]
[[Category:Science software for macOS]]
[[Category:Science software for Windows]]
[[Category:Mathematical and theoretical biology]]
[[Category:Mathematical and theoretical biology]]
[[Category:Computational biology]]
[[Category:Computational biology]]
[[Category:Cross-platform software]]
[[Category:Cross-platform software]]
[[Category:Biomedical cybernetics]]
[[Category:Biomedical cybernetics]]
[[Category:Simulation software]]
[[Category:Human homeostasis]]
[[Category:Human homeostasis]]
[[Category:Thyroid homeostasis]]
[[Category:Thyroid homeostasis]]

Latest revision as of 05:39, 9 August 2024

Original author(s)Johannes W. Dietrich, Ulla Mitzdorf, Renate Pickardt, Rudolf Hoermann, John E. M. Midgley
Developer(s)Ruhr University Bochum
Initial release2002 (22 years ago) (2002)
Stable release
4.0.6 / April 23, 2022; 2 years ago (2022-04-23)
Repository
Written inPascal and Object Pascal
Operating systemmacOS, Windows and Linux
PlatformPowerPC, IA-32, x86-64 and ARM,
m68k (legacy versions only)
Available inBritish English, German (SimThyr 2.0 or older only)
TypFree scientific application software for physiological simulations
LicenseBSD-style
Websitesimthyr.sourceforge.net Edit this on Wikidata

SimThyr is a free continuous dynamic simulation program for the pituitary-thyroid feedback control system.[1] The open-source program is based on a nonlinear model of thyroid homeostasis.[2][3][4] In addition to simulations in the time domain the software supports various methods of sensitivity analysis. Its simulation engine is multi-threaded and supports multiple processor cores. SimThyr provides a GUI, which allows for visualising time series, modifying constant structure parameters of the feedback loop (e.g. for simulation of certain diseases), storing parameter sets as XML files (referred to as "scenarios" in the software) and exporting results of simulations in various formats that are suitable for statistical software. SimThyr is intended for both educational purposes and in-silico research.[4][5]

Mathematical model

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The underlying model of thyroid homeostasis is based on fundamental biochemical, physiological and pharmacological principles, e.g. Michaelis-Menten kinetics, non-competitive inhibition and empirically justified kinetic parameters.[1] The model has been validated in healthy controls and in cohorts of patients with hypothyroidism and thyrotoxicosis.[6]

Scientific uses

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SimThyr used for educational purposes in a computer resource centre

Multiple studies have employed SimThyr for in silico research on the control of thyroid function.[7][8]

The original version was developed to check hypotheses about the generation of pulsatile TSH release.[9] Later and expanded versions of the software were used to develop the hypothesis of the TSH-T3 shunt in the hypothalamus-pituitary-thyroid axis,[10] to assess the validity of calculated parameters of thyroid homeostasis (including SPINA-GT and SPINA-GD)[11][12] and to study allostatic mechanisms leading to non-thyroidal illness syndrome.[13][14]

SimThyr was also used to show that the release rate of thyrotropin is controlled by multiple factors other than T4 and that the relation between free T4 and TSH may be different in euthyroidism, hypothyroidism and thyrotoxicosis.[15]

Public perception, reception and discussion of the software

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SimThyr is free and open-source software. This ensures the source code to be available, which facilitates scientific discussion and reviewing of the underlying model.[16][17] Additionally, the fact that it is freely available may result in economical benefits.[18][19]

The software provides an editor that enables users to modify most structure parameters of the information processing structure.[20] This functionality fosters simulation of several functional diseases of the thyroid and the pituitary gland. Parameter sets may be stored as MIRIAM- and MIASE-compliant XML files.

On the other hand, the complexity of the user interface and the lack of the ability to model treatment effects have been criticized.[21]

See also

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References

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  1. ^ a b Dietrich, JW; Landgrafe, G; Fotiadou, EH (2012). "TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis". Journal of Thyroid Research. 2012: 351864. doi:10.1155/2012/351864. PMC 3544290. PMID 23365787.
  2. ^ Hoermann, R; Midgley, JE; Larisch, R; Dietrich, JW (2015). "Homeostatic Control of the Thyroid-Pituitary Axis: Perspectives for Diagnosis and Treatment". Frontiers in Endocrinology. 6: 177. doi:10.3389/fendo.2015.00177. PMC 4653296. PMID 26635726.
  3. ^ Berberich, Julian (13 September 2018). "Mathematical Modeling of the Pituitary-Thyroid Feedback Loop: Matlab/Simulink Files for Simulation and Sensitivity Analysis". doi:10.5281/zenodo.1415331. {{cite journal}}: Cite journal requires |journal= (help)
  4. ^ a b Dietrich, Johannes W. (2002). Der Hypophysen-Schilddrüsen-Regelkreis : Entwicklung und klinische Anwendung eines nichtlinearen Modells. Berlin: Logos-Verlag. ISBN 978-3897228504.
  5. ^ Dietrich, Johannes W.; Midgley, John E. M.; Hoermann, Rudolf (2018). Homeostasis and Allostasis of Thyroid Function. Lausanne: Frontiers Media SA. ISBN 9782889455706.
  6. ^ Hoermann, R; Pekker, MJ; Midgley, JEM; Larisch, R; Dietrich, JW (February 2020). "Triiodothyronine secretion in early thyroid failure: The adaptive response of central feedforward control". European Journal of Clinical Investigation. 50 (2): e13192. doi:10.1111/eci.13192. PMID 31815292. S2CID 208956920.
  7. ^ Ramos, André; Chaves, Rafael; Favero, Elói (11 November 2019). "Simulação baseada em Dinâmica de Sistemas para o ensino da fisiologia do eixo Hipotálamo-hipófise-tireoide no contexto da graduação em medicina". Brazilian Symposium on Computers in Education (Simpósio Brasileiro de Informática Na Educação - SBIE) (in Portuguese). 30 (1): 962. doi:10.5753/cbie.sbie.2019.962. ISSN 2316-6533. S2CID 213401607.
  8. ^ Ghosh, Devleena; Mandal, Chittaranjan (2020). "Clustering Based Parameter Estimation of Thyroid Hormone Pathway". IEEE/ACM Transactions on Computational Biology and Bioinformatics. PP (1): 343–354. doi:10.1109/TCBB.2020.2995589. PMID 32750849. S2CID 219479222.
  9. ^ DIETRICH, J. W.; TESCHE, A.; PICKARDT, C. R.; MITZDORF, U. (2004). "Thyrotropic Feedback Control: Evidence for an Additional Ultrashort Feedback Loop from Fractal Analysis". Cybernetics and Systems. 35 (4): 315–331. doi:10.1080/01969720490443354. S2CID 13421388.
  10. ^ 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". Horm Metab Res. 47 (9): 674–80. doi:10.1055/s-0034-1398616. PMID 25750078. S2CID 9824656.
  11. ^ 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. 7: 57. doi:10.3389/fendo.2016.00057. PMC 4899439. PMID 27375554.
  12. ^ Hoermann, Rudolf; Midgley, John E. M.; Larisch, Rolf; Dietrich, Johannes W. (October 2018). "The role of functional thyroid capacity in pituitary thyroid feedback regulation". European Journal of Clinical Investigation. 48 (10): e13003. doi:10.1111/eci.13003. PMID 30022470. S2CID 51698223.
  13. ^ Hoermann, R; Midgley, JE; Larisch, R; Dietrich, JW (February 2013). "Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?". European Journal of Endocrinology. 168 (2): 271–80. doi:10.1530/EJE-12-0819. PMID 23184912. S2CID 34158774.
  14. ^ Chatzitomaris, A; Hoermann, R; Midgley, 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. 8: 163. doi:10.3389/fendo.2017.00163. PMC 5517413. PMID 28775711.
  15. ^ Midgley, JE; Hoermann, R; Larisch, R; Dietrich, JW (April 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. doi:10.1136/jclinpath-2012-201213. PMID 23423518. S2CID 46291947. Retrieved 4 December 2018.
  16. ^ Gezelter, Dan. "SimThyr – simulation software for pituitary thyroid feedback | The OpenScience Project". The OpenScience Project. Archived from the original on 4 April 2019. Retrieved 6 February 2019.
  17. ^ Glensbo, Henrik. "Fokus i 2020 - stofskiftesygdom.dk". www.stofskiftesygdom.dk. Stofskiftesygdom. Retrieved 2 April 2020.
  18. ^ Lupínek, Jiří (2012). Freeware simulační a vizualizační nástroje pro GNU/Linux (in Czech). Západočeská univerzita v Plzni. hdl:11025/5282.
  19. ^ 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.]". Hacettepe Sağlık İdaresi Dergisi. 17: 119–31.
  20. ^ Dietrich, J. W. (2017), SimThyr 4.0 Handbook and Reference, figshare, doi:10.6084/m9.figshare.4902098
  21. ^ Han, Simon Xian He (2013). THYROSIM: A Web Application for Human Thyroid System Regulation Education and Research (Thesis). Los Angeles: UCLA.
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