Understanding the Healthy Thyroid State in 2015.

Thyroid hormones (TH) are of crucial importance for the physiological function of almost all organs. In cases of abnormal TH signaling, pathophysiological consequences may arise. The routine assessment of a healthy or diseased thyroid function state is currently based on the determination of serum concentrations of thyroid-stimulating hormone (TSH), and the TH T3 and T4. However, the definition of a 'normal' TSH range and similarly 'normal' T3 and T4 concentrations remains the subject of debate in different countries worldwide and has important implications on patient treatment in clinics. Not surprisingly, a significant number of patients whose thyroid function tests are biochemically determined to be within the normal range complain of impaired well-being. The reasons for this are so far not fully understood, but it has been recognized that thyroid function status needs to be 'individualized' and extended beyond simple TSH measurement. Thus, more precise and reliable parameters are required in order to optimally define the healthy thyroid status of an individual, and as a perspective to employ these in clinical routine. With the recent identification of new key players in TH action, a more accurate assessment of a patient's thyroid status may in the future become possible. Recently described distinct TH derivatives and metabolites, TH transporters, nongenomic TH effects (either through membrane-bound or cytosolic signaling), and classical nuclear TH action allow for insights into molecular and cellular preconditions of a healthy thyroid state. This will be a prerequisite to improve management of thyroid dysfunction, and additionally to prevent and target TH-related nonthyroid disease.