[SPINA] Recent paper suggests hypothyroidism, euthyroidism and hyperthyroidism to be different homeostatic conditions

[sam goede]

Dear Johannes,

Could you send me a copy of this paper?

Best regards,

Sam


Op 19-3-2013 21:34, Johannes W. Dietrich schreef:
> Recently, a new paper using SPINA has been published in the Journal of 
> Clinical Pathology. By combining in-silico modelling using SimThyr 
> with an observation study in a large clinical sample (n=6641) it could 
> be demonstrated that TSH levels are not unambiguously coupled to FT4 
> levels. To add even more complexity, GT values in different ranges 
> were associated with a different influence of structure parameters on 
> TSH levels in sensitivity analysis.
>
> These observations question the log-linear standard model of thyroid 
> homeostasis and suggest that a hierarchically structured model of the 
> hypothalamic pituitary thyroid interaction may be a more appropriate 
> description of pituitary thyrotroph physiology.
>
> The results of this study are of considerable importance for 
> diagnostic evaluation of thyroid homeostasis, since they demonstrate 
> that a pure TSH-centric approach may be inadequate for diagnosis of 
> thyroid function in some, if not most, affected patients.
>
>
> Abstract:
> Aims: Understanding the exact relationship between serum 
> thyrotropin/thyroid stimulating hormone (TSH) and free thyroxine (FT4) 
> is a prerequisite for improving diagnostic reliability and clinical 
> decision making.
>
> Methods: We (1) retrospectively studied the relationship between TSH 
> and FT4 in a large unselected clinical sample (n=6641) of primary 
> hypothyroid, euthyroid and hyperthyroid subjects, and (2) applied a 
> mathematical model of thyroid hormone feedback control to assess the 
> relation between structural parameters and TSH levels in the different 
> functional states.
>
> Results: When separately analysing total sample and untreated 
> subjects, the correlation slope for logTSH versus FT4 for hypothyroid 
> subjects was significantly different from that of the euthyroid panel 
> and hyperthyroid subjects (the latter being compromised by reaching 
> the TSH assay's lower detection limit). As trends between functional 
> states changed, each functional segment appeared to become differently 
> regulated. Theoretical modelling and sensitivity analysis revealed 
> that the influence of various structural parameters on TSH levels also 
> depends on the overall function of the feedback loop.
>
> Conclusions: Our data suggest that the states of hypothyroidism, 
> euthyroidism and hyperthyroidism can be regarded as differently 
> regulated entities. The apparent complexity could be replicated by 
> mathematical modelling suggesting a hierarchical type of feedback 
> regulation involving patterns of operative mechanisms unique to each 
> condition. For clinical purposes and assay evaluation, neither the 
> standard model relating logTSH with FT4, nor an alternative model 
> based on non-competitive inhibition can be reliably represented by a 
> single correlation comparing all samples for both hormones in one 
> all-inclusive group.
>
> Citation and Access:
> Midgley JE, Hoermann R, Larisch R, Dietrich JW. [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.](http://jcp.bmj.com/content/66/4/335.abstract) J 
> Clin Pathol. 2013 Apr;66(4):335-342. Epub 2013 Feb 19. [PMID 
> 23423518](http://www.ncbi.nlm.nih.gov/pubmed/23423518), [doi 
> 10.1136/jclinpath-2012-201213](http://dx.doi.org/10.1136/jclinpath-2012-201213).
>
>
>
>
> -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- --
> -- Dr. Johannes W. Dietrich, M.D.
> -- Laboratory XU44, Endocrine Research
> -- Medical Hospital I, Bergmannsheil University Hospitals
> -- Ruhr University of Bochum
> -- Buerkle-de-la-Camp-Platz 1, D-44789 Bochum, NRW, Germany
> -- Phone: +49:234:302-6400, Fax: +49:234:302-6403
> -- eMail: "j.w.dietrich at medical-cybernetics.de 
> <mailto:j.w.dietrich at medical-cybernetics.de>"
> -- WWW: http://medical-cybernetics.de
> -- WWW: http://www.bergmannsheil.de
> -- Researcher ID: C-3498-2009
> -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- --
>
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