<html><body style="word-wrap: break-word; -webkit-nbsp-mode: space; -webkit-line-break: after-white-space; "><div>A paper about medical decision making in patients receiving substitution therapy with levothyroxine was published in the European Journal of Endocrinology (2013: 168: 271-80). The paper that made use of the MiMe-NoCoDI model of pituitary-thyroid feedback control demonstrated that a pure TSH-centered approach may be insufficient for assessment of thyroid state in certain forms of heterostasis. Sensitivity analysis with SimThyr 3.2 showed a strong influence of various structural parameters on TSH secretion.</div><div><br></div><div><br></div><div>Abstract:</div><div>Objective. In recognition of its primary role in pituitary-thyroid feedback, thyrotropin (TSH) determination has become a key parameter for clinical decision-making. The present study evaluates the value of TSH as a measure of thyroid hormone homeostasis under T4 therapy.</div><div>Design, Methods. We have examined the interrelationships between free triiodothyronine (FT3), free thyroxine (FT4) and pituitary TSH by means of 1) a retrospective analysis of a large clinical sample comprising 1994 patients either untreated or on varying doses of L-T4 and 2) independent mathematical simulation applying a model of thyroid homeostasis, together with a sensitivity analysis.</div><div>Results. Over a euthyroid to mildly hyperthyroid functional range, we found markedly different correlation slopes of log TSH versus FT3 and FT4 between untreated patients and L-T4 groups. Total deiodinase activity (GD) was positively correlated with TSH in untreated subjects. However, GD was significantly altered and the correlation lost under increasing L-T4 doses. 95% confidence intervals for FT3 and FT4, when assessed in defined TSH concentration bands, differed significantly for L-T4-treated, compared to untreated patients. Higher doses were often needed to restore FT3 levels within its reference range. Sensitivity analysis revealed the influence of various structural parameters on pituitary TSH secretion including a preeminent role of pituitary deiodinase type 2.</div><div>Conclusion. The data reveal disjoints between FT4-TSH feedback and T3 production that persist even when sufficient T4 apparently restores euthyroidism. T4 treatment displays a compensatory adaptation, but does not completely re-enact normal euthyroid physiology. This invites a study of the clinical consequences of this disparity.</div><div><br></div><div><br></div><div>Citation and Access:</div><div>Hoermann, R., J. E. M. Midgley, R. Larisch, J. W. Dietrich (2012). [Is Pituitary Thyrotropin an Adequate Measure Of Thyroid Hormone-Controlled Homeostasis During Thyroxine Treatment?](<a href="http://dx.doi.org/10.1530/EJE-12-0819">http://dx.doi.org/10.1530/EJE-12-0819</a>). European Journal of Endocrinology 168(2):271-80. [doi: 10.1530/EJE-12-0819](<a href="http://dx.doi.org/10.1530/EJE-12-0819">http://dx.doi.org/10.1530/EJE-12-0819</a>)</div><div><br></div><div apple-content-edited="true"> <span class="Apple-style-span" style="border-collapse: separate; color: rgb(0, 0, 0); font-family: Helvetica; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-align: -webkit-auto; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-border-horizontal-spacing: 0px; -webkit-border-vertical-spacing: 0px; -webkit-text-decorations-in-effect: none; -webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; font-size: medium; "><div style="word-wrap: break-word; -webkit-nbsp-mode: space; -webkit-line-break: after-white-space; "><span class="Apple-style-span" style="border-collapse: separate; color: rgb(0, 0, 0); font-family: Helvetica; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-align: -webkit-auto; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-border-horizontal-spacing: 0px; -webkit-border-vertical-spacing: 0px; -webkit-text-decorations-in-effect: none; -webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; font-size: medium; "><div style="word-wrap: break-word; -webkit-nbsp-mode: space; -webkit-line-break: after-white-space; "><span class="Apple-style-span" style="border-collapse: separate; color: rgb(0, 0, 0); font-family: Helvetica; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-align: -webkit-auto; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-border-horizontal-spacing: 0px; -webkit-border-vertical-spacing: 0px; -webkit-text-decorations-in-effect: none; -webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; font-size: medium; "><div style="word-wrap: break-word; -webkit-nbsp-mode: space; -webkit-line-break: after-white-space; "><span class="Apple-style-span" style="border-collapse: separate; color: rgb(0, 0, 0); font-family: Helvetica; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-border-horizontal-spacing: 0px; -webkit-border-vertical-spacing: 0px; -webkit-text-decorations-in-effect: none; -webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; font-size: medium; "><div><div><div><font class="Apple-style-span" size="2"><span class="Apple-style-span" style="font-size: 10px; "><br class="Apple-interchange-newline">-- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- --</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 class="Apple-style-span" style="font-size: 10px; ">-- Medical Hospital I, Bergmannsheil University Hospitals</span></font></div><div><font class="Apple-style-span" size="2"><span class="Apple-style-span" style="font-size: 10px; ">-- Ruhr University of Bochum</span></font></div><div><font class="Apple-style-span" size="2"><span class="Apple-style-span" style="font-size: 10px; ">-- Buerkle-de-la-Camp-Platz 1, D-44789 Bochum, NRW, Germany</span></font></div><div><font class="Apple-style-span" size="2"><span class="Apple-style-span" style="font-size: 10px; ">-- Phone: +49:234:302-6400, Fax: +49:234:302-6403</span></font></div><div><font class="Apple-style-span" size="2"><span class="Apple-style-span" style="font-size: 10px; ">-- eMail: "<a href="mailto:j.w.dietrich@medical-cybernetics.de">j.w.dietrich@medical-cybernetics.de</a>"</span></font></div><div><font class="Apple-style-span" size="2"><span class="Apple-style-span" style="font-size: 10px; ">-- WWW: <a href="http://medical-cybernetics.de">http://medical-cybernetics.de</a></span></font></div><div><font class="Apple-style-span" size="2"><span class="Apple-style-span" style="font-size: 10px; ">-- WWW: <a href="http://www.bergmannsheil.de">http://www.bergmannsheil.de</a></span></font></div></div></div></span></div></span></div></span><span class="Apple-style-span" style="border-collapse: separate; color: rgb(0, 0, 0); font-family: Helvetica; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-align: -webkit-auto; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-border-horizontal-spacing: 0px; -webkit-border-vertical-spacing: 0px; -webkit-text-decorations-in-effect: none; -webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; font-size: medium; "><div style="word-wrap: break-word; -webkit-nbsp-mode: space; -webkit-line-break: after-white-space; "><span class="Apple-style-span" style="border-collapse: separate; color: rgb(0, 0, 0); font-family: Helvetica; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-align: -webkit-auto; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-border-horizontal-spacing: 0px; -webkit-border-vertical-spacing: 0px; -webkit-text-decorations-in-effect: none; -webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; font-size: medium; "><div style="word-wrap: break-word; -webkit-nbsp-mode: space; -webkit-line-break: after-white-space; "><span class="Apple-style-span" style="border-collapse: separate; color: rgb(0, 0, 0); font-family: Helvetica; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-border-horizontal-spacing: 0px; -webkit-border-vertical-spacing: 0px; -webkit-text-decorations-in-effect: none; -webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; font-size: medium; "><div><div><div><font class="Apple-style-span" size="2"><span class="Apple-style-span" style="font-size: 10px; ">-- Researcher ID: C-3498-2009</span></font></div><div><font class="Apple-style-span" size="2"><span class="Apple-style-span" style="font-size: 10px; ">-- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- --</span></font></div></div></div></span><br><span class="Apple-style-span" style="border-collapse: separate; color: rgb(0, 0, 0); font-family: Helvetica; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-border-horizontal-spacing: 0px; -webkit-border-vertical-spacing: 0px; -webkit-text-decorations-in-effect: none; -webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; font-size: medium; "><div><br></div></span></div></span></div></span><br class="Apple-interchange-newline"></div></span><br class="Apple-interchange-newline"> </div><br></body></html>