[Biomedical-cybernetics] Paper published on diagnostic evaluation of thyroid homeostasis

[Johannes W. Dietrich]

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.


Abstract:
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.
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.
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.
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.


Citation and Access:
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?](http://dx.doi.org/10.1530/EJE-12-0819 
). European Journal of Endocrinology 168(2):271-80. [doi: 10.1530/ 
EJE-12-0819](http://dx.doi.org/10.1530/EJE-12-0819)


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-- 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"
-- WWW: http://medical-cybernetics.de
-- WWW: http://www.bergmannsheil.de
-- Researcher ID: C-3498-2009
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