The Hypothalamic-Pituitary-Thyroid Axis: Physiological Regulation and Clinical Implications

Thyroid hormone (TH) is essential for normal growth and differentiation as well as control of energy homeostasis and metabolism during adult life. Tight regulation of the thyroid function can be achieved through the development of the hypothalamic-pituitary-thyroid (HPT) axis, a neuroendocrine loop consisting of a negative feedback mechanism between circulating TH levels and the hypothalamus and pituitary gland. When circulating TH levels are low, the HPT axis is activated simultaneously at multiple levels to increase both the TRH production in the hypothalamus and the TSH production in pituitary. The entire HPT axis is suppressed when circulating TH levels are high. The effects of TH in the hypothalamus and pituitary are primarily mediated by T3, the majority of T3 being produced locally in the presence of type 2 deiodinase (DIO2) from circulating T4. Each individual has a physiological HPT axis set point determined mainly by genetic factors where it functions optimally.