A physiological mathematical model of the human thyroid

The thyroid is one of the largest endocrine glands in humans. The thyroid produces two major hormones: thyroxine (T4) and triiodothyronine (T3). The secretion and production of thyroid hormones are controlled via two feedbacks: one positive, where the thyrotropin-releasing hormone (TRH) stimulates the thyroid-stimulating hormone (TSH) that stimulates the production of T3 and T4 hormones; one negative, where high circulating levels of T3 and T4 in turn inhibit the production of both TRH and TSH. T3 and T4 also depend on iodine intake. The present work proposes a comprehensive mathematical model of the thyroid and TSH control system through which both the effect of the hormones and of iodine can be assessed. The proposed model is composed of 22 compartments, which describe the dynamics of iodine, T3, T4, TSH, TRH and Thyroglobulin (Tg) in blood and in the extra-cellular space. The effect of Sodium Iodide Symporter (NIS, a membrane protein mediating iodide transport) and of Thyroperoxidase (TPO, an enzyme involved in the thyroid hormone synthesis) on thyroid metabolism is also described and a gastrointestinal sub-model is incorporated in order to describe the oral administration of iodine, levothyroxine (L-T4) and levothyronine (L-T3). TSH oscillations are described using a series of impulses generated by a biological oscillator. The model has been validated on several independent data sets retrieved from the literature, where euthyroid volunteers underwent different clinical experiments with the oral administration of L-T4 (in 400, 450, 600 ug dosages) or L-T3 (75 ug) and with intravenous injections of TRH.