Hypothalamic–pituitary–thyroid axis

The hypothalamic–pituitary–thyroid axis (HPT axis for short, aka thyroid homeostasis or thyrotropic feedback control) is part of the endocrine system responsible for the regulation of metabolism.

As its name suggests, it depends upon the hypothalamus, the pituitary gland, and the thyroid gland.

The hypothalamus senses low circulating levels of thyroid hormone (T3 and T4) and responds by releasing thyrotropin-releasing hormone (TRH). The TRH stimulates the pituitary to produce thyroid-stimulating hormone (TSH). The TSH, in turn, 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.

Contents 1 Physiology 2 Functional states of thyrotropic feedback control 3 Diagnostics 4 See also 5 References 6 Additional References

Physiology

Thyroid homeostasis results from a multi-loop feedback system that is found in virtually all higher vertebrates. Proper function of thyrotropic feedback control is indispensable for growth, differentiation, reproduction and intelligence. Very few animals (e.g. axolotls and sloths) have impaired thyroid homeostasis that exhibits a very low set-point that is assumed to underlie the metabolic and ontogenetic anomalies of these animals.

The pituitary gland secretes thyrotropin (TSH) that stimulates the thyroid to secrete thyroxine (T4) and, to a lesser degree, triiodothyronine (T3). The major portion of T3, however, is produced in peripheral organs, e.g. liver, adipose tissue, glia and skeletal muscle by deiodination from circulating T4. Deiodination is controlled by numerous hormones and nerval signals including TSH, vasopressin and catecholamines.

Both peripheral thyroid hormones (iodothyronines) inhibit thyrotropin secretion from the pituitary (negative feedback). Consecutively, equilibrium concentrations for all hormones are attained.

TSH secretion is also controlled by thyrotropin releasing hormone (thyroliberin, TRH), whose secretion itself is again suppressed by plasma T4 and T3 in CSF (long feedback, Fekete–Lechan loop). Addtional feedback loops are ultrashort feedback control of TSH secretion (Brokken-Wiersinga-Prummel loop) and linear feedback loops controlling plasma protein binding.

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 hypodeiodination or hyperdeiodination, e.g. in critical illness.
• Thyroid hormone resistance: Feedback loop interrupted on the level of pituitary thyroid hormone receptors.

Diagnostics

Standard procedures cover the determination of serum levels of the following hormones:

• 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)^[3]
• Sum activity of peripheral deiodinases (GD)^[3]
• TSH Index (TSHI)^[4]

See also

• Thyroid function tests

References

1. ^ References used in overview figure are found in image article in Commons: References.
2. ^ References used in detailled figure are found in image article in Commons: References.
3. ^ ^{a b} Dietrich, J. W. (2002), Der Hypophysen-Schilddrüsen-Regelkreis, Berlin, Germany: Logos-Verlag Berlin, ISBN 978-3-89722-850-4, OCLC 50451543, 3897228505, http://openlibrary.org/books/OL24586469M/Der_Hypophysen-Schilddrüsen-Regelkreis 
4. ^ Jostel A, Ryder WD, Shalet SM. The use of thyroid function tests in the diagnosis of hypopituitarism: definition and evaluation of the TSH Index. Clin Endocrinol (Oxf). 2009 Oct;71(4):529-34. PMID 19226261.

Additional References

• J. W. Dietrich, A. Tesche, C. R. Pickardt, U. Mitzdorf: "Thyrotropic Feedback Control: Evidence for an Additional Ultrashort Feedback Loop from Fractal Analysis", in: Cybernetics and Systems, 2004, 35 (4), S. 315–331; doi:10.1080/01969720490443354.
• C. Gauna, G. H. van den Berghe, A. J. van der Lely: "Pituitary Function During Severe and Life-threatening Illnesses", in: Pituitary, 2005, 8 (3–4), S. 213–217; doi:10.1007/s11102-006-6043-3.

Human anatomy, endocrine system: endocrine glands (TA A11, TH H3.08, GA 11.1269) Islets of pancreas Alpha cell · Beta cell · Delta cell · PP cell · Epsilon cell Hypothalamic/ pituitary axes +parathyroid Pituitary Posterior pituitary Pars nervosa · Median eminence · Infundibular stalk Pituicyte · Herring bodies Anterior pituitary Pars intermedia · Pars tuberalis · Pars distalis Acidophil cell (Somatotropic cell, Prolactin cell) · Basophil cell (Corticotropic cell, Gonadotropic cell, Thyrotropic cell) · Chromophobe cell Thyroid axis Thyroid gland Thyroid isthmus · Lobes of thyroid gland · Pyramidal lobe of thyroid gland Follicular cell · Parafollicular cell Parathyroid gland Chief cell · Oxyphil cell Adrenal axis: Adrenal gland Cortex Zona glomerulosa · Zona fasciculata · Zona reticularis Medulla Medullary chromaffin cell Gonadal axis Gonad: Testes · Ovaries · Corpus luteum Pineal gland Pinealocyte · Corpora arenacea Other Enteroendocrine cell · Paraganglia M: END anat/phys/devp/horm noco(d)/cong/tumr, sysi/epon proc, drug (A10/H1/H2/H3/H5)