The mathematical model proposed focuses on the description of the behavior of the interaction between thyrotropin (i.e. thyroid-stimulating hormone (TSH)) and thyroid hormones with the objective of providing a better understanding of the behavior of TSH-T4 relationship in health and in disease. The normal pituitary-thyroid axis is tightly coupled and regulated with a servomechanism. In the physiological situation, any elevation of thyroid hormones will inhibit TSH secretion by the thyrotrophs of the pituitary, which in turn lead to an appropriate reduction in stimulation of the thyroid, accompanied by a decline of thyroid hormones towards normal. Similarly, a decline in thyroid hormones represents a potent input signal that when sensed by the pituitary thyrotrophs, will result in an increase of TSH output by the latter to accelerate the synthesis and secretion of thyroid hormones to drive the state towards normal equilibrium. Using this model, the profound sensitivity of thyrotrophs to feedback by thyroid hormones can be appreciated and understood better in the context of diseases of thyroid hormone excess and deficiency.