Hoermann R, et al. - In silico analysis and in vivo data was combined to investigate the central influences on thyroidal T3 production. Using a physiologically-based mathematical model of combined feedback-feedforward control of the hypothalamic-pituitary-thyroid regulation, dependencies exhibited in the expression of control vary in thyroid health and disease. When glandular T3 secretion becomes frequently influential over conversion competence, robust T3-protective mechanisms of the control system emerged with decreasing thyroid function. Moreover, for the use of TSH in clinical decision making, this has wide-ranging indications.