Biomedical Cybernetics

Thyrotropic feedback control (TFC, a. k. a. pituitary-thyroid axis) in vertebrates controls the secretion of classical thyroid hormones (iodothyronines) by means of the control hormone TSH (and possibly additional hormones like thyrostimulin). As thyroid hormones play an important role for metabolism, growth and differentiation, exact regulation of thyroid hormone levels is vital for most organisms.

History of research[]

In 1940, eleven years after the discovery of the thyrotropic hormone TSH by Aron in the year 1929, W. T. Salter postulated the existence of a control loop linking the pituitary and thyroid gland. This idea was inspired by the recent description of the two gonadotropic feedback control loops. Only a few years later, Astwood and Hoskins could reveal both the existence and the pathophysological relevance of this thyrotropic feedback control system. In 1968, Panda and Turner succeeded in a quantitative description ot the interdependence of thyroxine and TSH levels, but the first mathematical models of the feedback loop had already been developed up to 12 years earlier.

Over the years, these models were increasingly improved. As a consequence of this continued evolution, some of the newest models [Dietrich 2002, Dietrich et al. 2004 and Eisenberg et al. 2008] are also suitable for clinical application like medical decision making, diagnostics (SPINA) and bioequivalence studies.

Today, modelling of thyrotropic feedback control is faced with the challenge of newly discovered complexities in the information processing structure, e. g. Ultrashort feedback control of TSH secretion (Kakita-Laborde-Odell loop and Brokken-Wiersinga-Prummel loop) and long-feedback of iodothyronines on hypothalamic TRH release (Fekete-Lechan loop).


  1. Kakita T, Odell WD. (1986). Pituitary gland: one site of ultrashort-feedback regulation for control of thyrotropin. Am J Physiol. 250(2 Pt 1):E121-4. PMID 3082213.
  2. Prummel MF, Brokken LJ, Meduri G, Misrahi M, Bakker O, Wiersinga WM.: Expression of the thyroid-stimulating hormone receptor in the folliculo-stellate cells of the human anterior pituitary. J Clin Endocrinol Metab. 2000 Nov;85(11):4347-53. PMID 11095478
  3. Brokken LJ, Scheenhart JW, Wiersinga WM, Prummel MF.: Suppression of serum TSH by Graves' Ig: evidence for a functional pituitary TSH receptor. J Clin Endocrinol Metab. 2001 Oct;86(10):4814-7. PMID 11600546
  4. Dietrich, J. W. (2002). Der Hypophysen-Schilddrüsen-Regelkreis. Entwicklung und klinische Anwendung eines nichtlinearen Modells. Berlin, Logos-Verlag.
  5. Brokken LJ, Wiersinga WM, Prummel MF.: Thyrotropin receptor autoantibodies are associated with continued thyrotropin suppression in treated euthyroid Graves' disease patients. J Clin Endocrinol Metab. 2003 Sep;88(9):4135-8. PMID 12970276
  6. Dietrich, J. W., A. Tesche, C. R. Pickardt und U. Mitzdorf (2004). "Thyrotropic Feedback Control: Evidence for an Additional Ultrashort Feedback Loop from Fractal Analysis." Cybernetics and Systems 35 (4): 315-31.
  7. Prummel MF, Brokken LJ, Wiersinga WM (2004): Ultra short-loop feedback control of thyrotropin secretion. Thyroid. 14(10): 825-9. PMID 15588378
  8. Lechan RM, Fekete C. (2004). Feedback regulation of thyrotropin-releasing hormone (TRH): mechanisms for the non-thyroidal illness syndrome. J Endocrinol Invest. 27(6 Suppl):105-19. Review. PMID 15481810.
  9. Brokken LJ, Bakker O, Wiersinga WM, Prummel MF (2005): Functional thyrotropin receptor expression in the pituitary folliculo-stellate cell line TtT/GF. Exp Clin Endocrinol Diabetes. 113(1): 13-20. PMID 15662590
  10. Leow MK. A mathematical model of pituitary--thyroid interaction to provide an insight into the nature of the thyrotropin--thyroid hormone relationship. J Theor Biol. 2007 Sep 21;248(2):275-87. Epub 2007 May 18. PMID 17602707.
  11. Eisenberg M, Samuels M, DiStefano JJ 3rd. (2008). Extensions, validation, and clinical applications of a feedback control system simulator of the hypothalamo-pituitary-thyroid axis. Thyroid. 18(10):1071-85. PMID 18844475; PMCID PMC2962855.
  12. Dietrich JW, Landgrafe G, Fotiadou EH. TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis. J Thyroid Res. 2012;2012:351864. doi: 10.1155/2012/351864. Epub 2012 Dec 30. PMID 23365787; PMCID PMC3544290.
  13. Hoermann R, Midgley JE, Larisch R, Dietrich JW. Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment? Eur J Endocrinol. 2013 Jan 17;168(2):271-80. doi: 10.1530/EJE-12-0819. Print 2013 Feb. PMID 23184912.
  14. Midgley JE, Hoermann R, Larisch R, Dietrich JW. 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. J Clin Pathol. 2013 Feb 19. [Epub ahead of print] PMID 23423518.

See also[]

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