Advanced Methodology and Clinical Application in Hormonal Feedback

Authors

Johannes W. Dietrich

Abstract

Not unlike other foundations of life the release of most, if not all, vertebrate hormones is controlled by characteristic information processing structures like feedback loops, antagonistic redundancy and reafference motifs. It is therefore not surprising that the development of systems theory and cybernetics between 1930 and 1950 ignited the transition to modern endocrinology. Today, principles of endocrinology used to be imparted on the base of systems models of homeostasis. Unfortunately, however, the potential of systems thinking is still not fully utilized for clinical decision-making. Therefore, reasoning in endocrinology continues to be restricted to pure statistics-based approaches that obstruct the pathway to personalised and participatory medicine.

This surprising unsuccessfulness of systems thinking in endocrinology goes back to four barriers. They include a low quality of the majority of published mathematical models, intellectual challenges that accompany construction and application of improved physiologically-based models, insufficient education of physicians in cybernetics and systems science, and a lack of practically useful clinical applications of systems models.

Luckily, we are today in the situation to have solutions for all four barriers. Key elements include the advent of new homeostatic models based on physiological and biochemical principles, a plethora of advanced methods from systems biology – e.g. powerful simulation platforms – and, recently, the development of techniques based on mathematical modelling that allow for diagnosis and treatment of endocrine diseases on an individualised basis. First clinical trials demonstrated the superiority of these novel methods over the previous purely statistic-based approaches.

The transition to systems endocrinology, which is also a recollection of old foundations, promises to pave the way to predictive, preventive, personalised and participatory (P4) medicine for patients suffering from highly prevalent diseases like obesity, type 2 diabetes or thyroid disorders.

This talk outlines principles of systems endocrinology. Beginning with physiological and biochemical foundations like pharmacokinetics, enzymology and receptor biology it illustrates typical network motifs and methods of mathematical modelling in systems endocrinology before it introduces the open-source project CyberUnits, a novel reusable cross-platform class library, which facilitates rapid programming of high-performance computer simulations in life sciences.

References

DiStefano III J (2013). Dynamic Systems Biology Modeling and Simulation. Academic Press, Amsterdam, Boston, Heidelberg, London. ISBN 978-0-12-410411-2. 

Dietrich JW, Landgrafe G, Fotiadou EH (2012). TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis. J Thyroid Res. 2012;2012:351864. doi: 10.1155/2012/351864. Epub 2012 Dec 30. PubMed PMID: 23365787; PubMed Central PMCID: PMC3544290. http://dx.doi.org/10.1155/2012/351864

Dietrich, JW, Böhm, BO (2006): Equilibrium behaviour of feedback-coupled physiological saturation kinetics. In R. Trappl (Ed). Cybernetics and Systems 2006. Austrian Society for Cybernetic Studies, pp.269-74. http://dx.doi.org/10.13140/2.1.2400.2568

Dietrich, JW (2005): Zwischen milieu intérieur und medical decision making – Aspekte einer medizinischen Kybernetik http://dx.doi.org/10.13140/2.1.3448.8325 

Dietrich, JW, Böhm, BO (2004): Antagonistic Redundancy – A Theory of Error-Correcting Information Transfer in Organisms. In R. Trappl (Ed). Cybernetics and Systems 2004. Austrian Society for Cybernetic Studies, pp.225-30. http://dx.doi.org/10.13140/2.1.1083.8728 

Stats

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.