A system designed solely for the purpose of perfect FT3 homeostasis could optimally translate its setting from top to bottom, but it would at the same time be firmly locked in by rigid mechanisms, lacking in flexibility, not recognising the need for adapting to new conditions [1]. Such a system, while well suited for the purpose of homeostasis, is rather unsupportive of allostasis and the transition to a new state with altered homeostatic levels when this may be more beneficial. An important goal of the thyroid system in all mammalian species is to synchronise transitions in the natural environment and their energetic and metabolic consequences [2]. These aspects seem to be particularly important in non-thyroidal diseases [3], but they may be equally relevant for persistent low-T3 states that are observed in hypothyroid patients treated with levothyroxine [4]. Therefore, the system of hypothalamic–pituitary–thyroid axis regulation requires additional mechanisms of homeostatic escape and allostatic adaption [1]. A mathematical framework and operational definitions are given in Chap. 4 .