Thyroid control loop

The thyrotropic control circuit (synonyms: pituitary-thyroid control circuit, pituitary-thyroid axis, thyroid axis) is a multi- loop control circuit between the hypothalamus , pituitary and thyroid gland . It regulates the concentration of thyroid hormones in the blood plasma .

physiology

Thyroid function control circuit: stimulating effect of the hormone + inhibiting effect of the hormone - (negative feedback)

The thyrotropic control loop (simplified representation)

The pituitary secretes the control hormone thyrotropin (TSH), which stimulates the secretion of thyroxine (T4) and triiodothyronine (T3) in the thyroid gland . These thyroid hormones for their part inhibit the production and release of TSH in the sense of a negative feedback , so that an equilibrium level of the amount of thyroid hormones in the blood is normally established. fT ₄ (free T ₄ ) is the decisive feedback signal for the inhibition of the secretion of thyrotropin, while the T ₃ concentration in the plasma according to current knowledge does not have its own inhibiting effect on the secretion of thyrotropin. T ₃ binds to a nuclear receptor on the thyretropin cells, thereby blocking the biosynthesis of TSH and TRH receptors. The production and release of TSH also depends on the level of the thyrotropin releasing hormone TRH and somatostatin , both of which are produced and released by the hypothalamus . The hypothalamus specifies the target value for the thyroid hormones in the blood and constantly measures the actual value . In order to adapt the actual value of the thyroid hormones in the blood to the target value of the thyroid hormones in the blood, the hypothalamus can influence the production amount of TRH and thus the production amount of TSH and thyroid hormones.

Apart from this main control loop , there are further feedback loops switched on , e.g. B. Ultra-short feedback from TSH on its own release (Brokken-Wiersinga-Prummel control loop), long feedback from thyroid hormones on the TRH release and control loops that adjust the plasma protein binding of T4 and T3.

Studies on large populations have shown that there is also an additional pre-control in humans that links the TSH level with the activity of deiodinases. This TSH-T3 shunt could explain why the total activity of peripheral deiodinases is higher in hypothyroid patients than in euthyroid patients and why a small proportion of those affected benefit from substitution therapy with T3.

In addition to TRH, somatostatin and peripheral thyroid hormones, TSH secretion is controlled by various other afferent signals. This is probably one of the reasons that the relationship between fT4 and TSH deviates from the log-linear relationship that was previously propagated.

The thyroid uptake of iodine is not only dependent on the TSH level, but is also subject to iodine-dependent autoregulation . A low concentration of iodine in the blood increases the uptake of iodine in the gastrointestinal tract and the uptake of iodine in the thyroid gland, even in the absence of TSH. In addition, the synthesis of thyroid hormones is also increased in the absence of TSH. Giving large amounts of iodide (several hundred milligrams - the daily requirement of a healthy person is specified by the WHO as 200 micrograms) inhibit iodide absorption, hormone synthesis and hormone secretion ( Wolff-Chaikoff effect , after Louis Wolff , 1898–1972, American cardiologist and IL Chaikoff, American physiologist). This effect, which lasts only a few days, was used in the past to treat hyperthyroidism prior to thyroid surgery (" plumming ", after Henry Stanley Plummer ).

Functional states of the pituitary-thyroid control circuit

• Euthyroidism (normal thyroid function)
• Hypothyroidism (underactive thyroid)
  • Primary hypothyroidism (control loop in the thyroid gland impaired, e.g. due to poor incretion performance after surgery or in the case of autoimmune thyroid disorders )
  • Secondary hypothyroidism (impaired control loop in the pituitary gland, e.g. as part of an anterior pituitary insufficiency )
  • Tertiary hypothyroidism (the target value is not specified due to a lack of TRH , e.g. in the context of damage to the hypothalamus , a Pickardt syndrome or a euthyroid sick syndrome .)
• Hyperthyroidism (overactive thyroid)
  • Primary hyperthyroidism (inappropriate secretion of thyroid hormones due to a disease of the thyroid gland, e.g. in autonomy and in Graves' disease )
  • Secondary hyperthyroidism (rarely caused by TSH-producing tumors of the pituitary gland or with thyroid hormone resistance )
  • Tertiary hyperthyroidism (conceivable due to overproduction of TRH in the hypothalamus or paraneoplastic TRH formation, not yet observed)
• Thyrotoxicosis (oversupply of thyroid hormones, e.g. due to excessive drug treatment of hypothyroidism)
• Thyroid hormone resistance (impairment of the control loop at the receptors in the pituitary gland or the periphery )

Diagnosis

In most cases, the function of the control loop can be determined by determining the following hormones :

• TSH (thyroid stimulating hormone)
• Free T4
• Free T3

The following thyroid function tests are only required for special questions :

• Total T4
• Total T3
• TRH
• TBG
• TRH tests
• Thyroid secretion capacity (GT)
• Total activity of peripheral deiodinases (GD)
• TSH index (TSHI)

literature

• MT McDermott, EC Ridgway: Central hyperthyroidism. In: Endocrinol Metab Clin North Am. 27 (1), Mar 1998, pp. 187-203. PMID 9534036
• JW Dietrich: The pituitary-thyroid control circuit. Development and clinical application of a non-linear model. Logos-Verlag, Berlin 2002, ISBN 3-89722-850-5 .
• JW Dietrich, A. Tesche, CR Pickardt, U. Mitzdorf: Thyrotropic Feedback Control: Evidence for an Additional Ultrashort Feedback Loop from Fractal Analysis. In: Cybernetics and Systems . 35 (4), 2004, pp. 315-331; doi: 10.1080 / 01969720490443354 .
• C. Gauna, GH van den Berghe, AJ van der Lely: Pituitary Function During Severe and Life-threatening Illnesses. In: Pituitary . 8 (3-4), 2005, pp. 213-217; doi: 10.1007 / s11102-006-6043-3 .

Individual evidence

1. ^ ^{A b} Hans-Christian Pape, Armin Kurtz, Stefan Silbernagl: Physiology . 7th edition. Georg Thieme Verlag, Stuttgart 2014, ISBN 978-3-13-796007-2 , p. 624 .
2. ^ JW Dietrich, G. Landgrafe, EH Fotiadou: TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis. In: J Thyroid Res. 2012, p. 351864. doi: 10.1155 / 2012/351864 . Epub 2012 Dec 30. PMID 23365787
3. ^ R. Hoermann, JE Midgley, A. Giacobino, WA Eckl, HG Wahl, JW Dietrich, R. Larisch: Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment . In: Clin Endocrinol (Oxf) . tape 81 , no. 6 , 2014, p. 907-915 , doi : 10.1111 / cen.12527 , PMID 24953754 .
4. ^ JW Dietrich, JE Midgley, R. Larisch, R. Hoermann: Of rats and men: thyroid homeostasis in rodents and human beings. In: The Lancet. Diabetes & Endocrinology . tape 3 , no. December 12 , 2015, p. 932-933 , doi : 10.1016 / S2213-8587 (15) 00421-0 , PMID 26590684 .
5. ^ R. Hoermann, JE Midgley, R. Larisch, JW Dietrich: Integration of Peripheral and Glandular Regulation of Triiodothyronine Production by Thyrotropin in Untreated and Thyroxine-Treated Subjects . In: Hormone and Metabolic Research . 2015, doi : 10.1055 / s-0034-1398616 , PMID 25750078 .
6. ^ S. Reichlin, RD Utiger: Regulation of the pituitary-thyroid axis in man: relationship of TSH concentration to concentration of free and total thyroxine in plasma. In: J Clin Endocrinol Metab . 27, 1967, pp. 251-255. PMID 4163614 .
7. ^ R. Hoermann, W. Eckl, C. Hoermann, R. Larisch: Complex relationship between free thyroxine and TSH in the regulation of thyroid function. In: Eur J Endocrinol. 162, 2010, pp. 1123-1129. doi: 10.1530 / EJE-10-0106 . PMID 20299491 .
8. ^ PM Clark, RL Holder, SM Haque, FD Hobbs, LM Roberts, JA Franklyn: The relationship between serum TSH and free T4 in older people. In: J Clin Pathol . 65, 2012, pp. 463-465. doi: 10.1136 / jclinpath-2011-200433 . PMID 22287691 .
9. ^ R. Hoermann, JE Midgley, R. Larisch, JW Dietrich: Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment? In: Eur J Endocrinol. 16, 2013, pp. 271-280. doi: 10.1530 / EJE-12-0819 . PMID 23184912 .
10. ↑ JE Midgley, R. Hoermann, R. Larisch, JW Dietrich: Physiological states and functional relation between thyrotropin and free thyroxine in thyroid health and disease: in vivo and in silico data suggest a hierarchical model. In: J Clin Pathol. 66, 2013, pp. 335-342. doi: 10.1136 / jclinpath-2012-201213 PMID 23423518
11. ^ Hans-Christian Pape, Armin Kurtz, Stefan Silbernagl: Physiology . 7th edition. Georg Thieme Verlag, Stuttgart 2014, ISBN 978-3-13-796007-2 , p. 625 .
12. ^ Wolff-Chaikoff effect. ( Memento from March 20, 2011 in the web archive archive.today ) at: jrank.org
13. ^ Roche Lexicon Medicine. 5th edition. Urban & Fischer Verlag, Munich 2003. P. iodine treatment (plummers). ( Memento from July 14, 2015 in the web archive archive.today )
14. ↑ T. Kuwert: Thyroid. In: T. Kuwert, F. Grünwald, U. Haberkorn, T. Krause: Nuclear medicine. Stuttgart / New York 2008, ISBN 978-3-13-118504-4 .

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !