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<font face="Arial">Dear Johannes,<br>
<br>
Could you send me a copy of this paper?<br>
<br>
Best regards,<br>
<br>
Sam<br>
<br>
<br>
</font>
<div class="moz-cite-prefix">Op 19-3-2013 21:34, Johannes W.
Dietrich schreef:<br>
</div>
<blockquote
cite="mid:ADE1FF75-C702-4969-99B7-1EFB293EA64C@ruhr-uni-bochum.de"
type="cite">
<div>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.</div>
<div><br>
</div>
<div>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.</div>
<div><br>
</div>
<div>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.</div>
<div><br>
</div>
<div><br>
</div>
<div>Abstract:</div>
<div>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. </div>
<div><br>
</div>
<div>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. </div>
<div><br>
</div>
<div>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. </div>
<div><br>
</div>
<div>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.</div>
<div><br>
</div>
<div>Citation and Access:</div>
<div>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.](<a
moz-do-not-send="true"
href="http://jcp.bmj.com/content/66/4/335.abstract">http://jcp.bmj.com/content/66/4/335.abstract</a>)
J Clin Pathol. 2013 Apr;66(4):335-342. Epub 2013 Feb 19. [PMID
23423518](<a moz-do-not-send="true"
href="http://www.ncbi.nlm.nih.gov/pubmed/23423518">http://www.ncbi.nlm.nih.gov/pubmed/23423518</a>),
[doi 10.1136/jclinpath-2012-201213](<a moz-do-not-send="true"
href="http://dx.doi.org/10.1136/jclinpath-2012-201213">http://dx.doi.org/10.1136/jclinpath-2012-201213</a>).</div>
<div><br>
</div>
<div><br>
</div>
<div><br>
</div>
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-- -- -- -- -- -- -- -- -- -- --</span></font></div>
<div><font class="Apple-style-span" size="2"><span
class="Apple-style-span" style="font-size:
10px; ">-- Dr. Johannes W. Dietrich, M.D.</span></font></div>
<div><font class="Apple-style-span" size="2"><span
class="Apple-style-span" style="font-size:
10px; ">-- Laboratory XU44, Endocrine
Research</span></font></div>
<div><font class="Apple-style-span" size="2"><span
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Bergmannsheil University Hospitals</span></font></div>
<div><font class="Apple-style-span" size="2"><span
class="Apple-style-span" style="font-size:
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