Hypothalamic–pituitary–thyroid axis
The hypothalamic–pituitary–thyroid axis (HPT axis for short, a.k.a. thyroid homeostasis or thyrotropic feedback control) is part of the
As its name suggests, it depends upon the
The hypothalamus senses low circulating levels of thyroid hormone (
The HPA, HPG, and HPT axes are three pathways in which the hypothalamus and pituitary direct neuroendocrine function.
Physiology
Thyroid homeostasis results from a multi-loop
The pituitary gland secretes
Both peripheral thyroid hormones (iodothyronines) inhibit thyrotropin secretion from the pituitary (negative feedback). Consequently, equilibrium concentrations for all hormones are attained.
TSH secretion is also controlled by
Recent research suggested the existence of an additional feedforward motif linking TSH release to deiodinase activity in humans.[6][7][8] The existence of this TSH-T3 shunt could explain why deiodinase activity is higher in hypothyroid patients and why a minor fraction of affected individuals may benefit from substitution therapy with T3.[9]
Convergence of multiple afferent signals in the control of TSH release including but not limited to T3,[10] cytokines[11][12] and TSH receptor antibodies[13] may be the reason for the observation that the relation between free T4 concentration and TSH levels deviates[14][15][16][17] from a pure loglinear relation that has previously been proposed.[18] Recent research suggests that ghrelin also plays a role in the stimulation of T4 production and the subsequent suppression of TSH directly and by negative feedback.[19]
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.
- primary hypothyroidism: Feedback loop interrupted by low thyroid secretory capacity, e.g. after thyroid surgery or in case of
- 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.
- posttraumatic stress disorder.[12]
- Resistance to thyroid hormone: Feedback loop interrupted on the level of pituitary thyroid hormone receptors.
Diagnostics
Standard procedures cover the determination of
- TSH (thyrotropin, thyroid stimulating hormone)
- Free T4
- Free T3
For special conditions the following assays and procedures may be required:
- Total T4
- Total T3
- TBG
- TRH test
- Thyroid's secretory capacity (GT)[21]
- Sum activity of peripheral deiodinases (GD)[21]
- TSH Index (TSHI)[22]
See also
- Thyroid function tests
- Hypothalamic–pituitary–adrenal axis
- Hypothalamic–pituitary–gonadal axis
- Hypothalamic–neurohypophyseal system
- SimThyr, a free computer simulation for thyroid homeostasis in humans
References
- ^ References used in overview figure are found in image article in Commons: References.
- PMID 23365787.
- ^ References used in detailed figure are found in image article in Commons: References.
- PMID 15481810.
- PMID 15588378.
- S2CID 19341039.
- PMID 26590684.
- PMID 26635726.
- S2CID 9824656.
- PMID 28794850.
- PMID 25005935.
- ^ PMID 28775711.
- PMID 12970276.
- PMID 20299491.
- S2CID 43886378.
- PMID 23184912.
- S2CID 46291947.
- PMID 4163614.
- S2CID 5237852.
- S2CID 35344744.
- ^ OL 24586469M. 3897228505.
- S2CID 10827131.
Further reading
- Dietrich J W, Tesche A, Pickardt C R, Mitzdorf U (2004). "Thyrotropic Feedback Control: Evidence for an Additional Ultrashort Feedback Loop from Fractal Analysis". S2CID 13421388.)
{{cite journal}}: CS1 maint: multiple names: authors list (link - Gauna C, van den Berghe G H, van der Lely A J (2005). "Pituitary Function During Severe and Life-threatening Illnesses". S2CID 22305001.)
{{cite journal}}: CS1 maint: multiple names: authors list (link - Dietrich, Johannes W.; Midgley, John E. M.; Hoermann, Rudolf (2018). Homeostasis and allostasis of thyroid function. Lausanne: Frontiers Media SA. ISBN 9782889455706.