Hypothalamic pituitary thyroid axis

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Clinic

  • HPT axis for short, a.k.a. thyroid homeostasis or thyrotropic feedback control is part of the neuroendocrine system responsible for the regulation of metabolism and also responds to stress.
  • Hypothalamus senses low circulating levels of T3 and T4 and responds by releasing TRH.
  • TRH stimulates the anterior pituitary to produce TSH.
  • TSH stimulates the thyroid to produce thyroid hormone until levels in the blood return to normal.
  • Thyroid hormone exerts negative feedback control over the hypothalamus as well as anterior pituitary, thus controlling the release of both TRH from hypothalamus and TSH from anterior pituitary gland.

HPA, HPG, and HPT axes are three pathways in which the hypothalamus and pituitary direct neuroendocrine function.

Functional states of thyrotropic feedback control

  • Euthyroidism: Normal thyroid function
  • Hypothyroidism: Reduced thyroid function
    • Primary hypothyroidism: Feedback loop interrupted by low thyroid secretory capacity, e.g. after thyroid surgery or in case of autoimmune thyroiditis
    • secondary hypothyroidism: Feedback loop interrupted on the level of pituitary, e.g. in anterior pituitary failure
    • Tertiary hypothyroidism: Lacking stimulation by TRH, e.g. in hypothalamic failure, Pickardt–Fahlbusch syndrome or euthyroid sick syndrome.
  • Hyperthyroidism: Inappropriately increased thyroid function
    • Primary hyperthyroidism: Inappropriate secretion of thyroid hormones, e.g. in case of Graves' disease.
    • Secondary hyperthyroidism: Rare condition, e.g. in case of TSH producing pituitary adenoma or partial thyroid hormone resistance.
  • Thyrotoxicosis: Over-supply with thyroid hormones, e.g. by overdosed exogenously levothyroxine supplementation.
  • Low-T3 syndrome and high-T3 syndrome: Consequences of step-up hypodeiodination, e.g. in critical illness as an example for type 1 allostasis, or hyperdeiodination, as in type 2 allostasis, including posttraumatic stress disorder.
  • Resistance to thyroid hormone: Feedback loop interrupted on the level of pituitary thyroid hormone receptors.