Hoermann R, et al. - This analysis was designed to examine the central influences on thyroidal T3 production. Researchers used a system of five coupled first-order nonlinear parameterized ordinary differential equations to model the feedback control of TSH and TRH by thyroid hormones together with the feedforward control of thyroidal T3 secretion and enzymatic T4-T3 conversion. Utilizing a physiologically based mathematical model of combined feedback-feedforward control of the hypothalamic-pituitary-thyroid regulation, dependencies showed in the expression of control differ in thyroid health and disease. The results suggested that when glandular T3 secretion becomes increasingly influential over conversion efficiency, strong T3-protective mechanisms of the control system emerge with diminishing thyroid function. Moreover, this has wide-ranging implications for the benefit of TSH in clinical decision-making.