AUTHOR=Berberich Julian , Dietrich Johannes W. , Hoermann Rudolf , Müller Matthias A. 

TITLE=Mathematical Modeling of the Pituitary–Thyroid Feedback Loop: Role of a TSH-T3-Shunt and Sensitivity Analysis

JOURNAL=Frontiers in Endocrinology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2018.00091

DOI=10.3389/fendo.2018.00091

ISSN=1664-2392

ABSTRACT=<p>Despite significant progress in assay technology, diagnosis of functional thyroid disorders may still be a challenge, as illustrated by the vague upper limit of the reference range for serum thyrotropin (<italic>TSH</italic>). Diagnostical problems also apply to subjects affected by syndrome T, i.e., those 10% of hypothyroid patients who continue to suffer from poor quality of life despite normal <italic>TSH</italic> concentrations under substitution therapy with levothyroxine (<italic>L</italic>-<italic>T</italic><sub>4</sub>). In this paper, we extend a mathematical model of the pituitary–thyroid feedback loop in order to improve the understanding of thyroid hormone homeostasis. In particular, we incorporate a <italic>TSH</italic>-<italic>T</italic><sub>3</sub>-shunt inside the thyroid, whose existence has recently been demonstrated in several clinical studies. The resulting extended model shows good accordance with various clinical observations, such as a circadian rhythm in free peripheral triiodothyronine (<italic>FT</italic><sub>3</sub>). Furthermore, we perform a sensitivity analysis of the derived model, revealing the dependence of <italic>TSH</italic> and hormone concentrations on different system parameters. The results have implications for clinical interpretation of thyroid tests, e.g., in the differential diagnosis of subclinical hypothyroidism.</p>