Thyrotroph Thyroid Hormone Sensitivity Index

Last updated
Thyrotroph Thyroid Hormone Sensitivity Index
Synonyms TTSI, Thyrotroph T4 Resistance Index, TT4RI
Reference range 100-150
Test ofSensitivity of TSH-producing pituitary cells to thyroid hormones; also a marker for the set point of thyroid homeostasis

The Thyrotroph Thyroid Hormone Sensitivity Index (abbreviated TTSI, also referred to as Thyrotroph T4 Resistance Index or TT4RI) is a calculated structure parameter of thyroid homeostasis. It was originally developed to deliver a method for fast screening for resistance to thyroid hormone. [1] [2] Today it is also used to get an estimate for the set point of thyroid homeostasis, [3] especially to assess dynamic thyrotropic adaptation of the anterior pituitary gland, including non-thyroidal illnesses. [4]

Contents

How to determine TTSI

Universal form

The TTSI can be calculated with

from equilibrium serum or plasma concentrations of thyrotropin (TSH), free T4 (FT4) and the assay-specific upper limit of the reference interval for FT4 concentration (lu). [4]

Reference ranges

ParameterLower limitUpper limitUnit
TTSI100150

Short form

Some publications use a simpler form of this equation that doesn't correct for the reference range of free T4. It is calculated with

.

The disadvantage of this uncorrected version is that its numeric results are highly dependent on the used assays and their units of measurement.[ citation needed ]

Biochemical associations

In case of resistance to thyroid hormone, the magnitude of TTSI depends on which nucleotide in the THRB gene is mutated, but also on the genotype of coactivators. A systematic investigation in mice demonstrated a strong association of TT4RI to the genotypes of THRB and the steroid receptor coactivator (SRC-1) gene. [5]

Clinical significance

The TTSI is used as a screening parameter for resistance to thyroid hormone due to mutations in the THRB gene, where it is elevated. [4] It is also beneficial for assessing the severity of already confirmed thyroid hormone resistance, [6] even on replacement therapy with L-T4, [7] and for monitoring the pituitary response to substitution therapy with thyromimetics (e.g. TRIAC) in RTH Beta. [8]

In autoimmune thyroiditis the TTSI is moderately elevated. [9]

A large cohort study demonstrated TTSI to be strongly influenced by genetic factors. [10] A variant of the TTSI that is not corrected for the upper limit of the FT4 reference range was shown to be significantly increased in offspring from long-lived siblings compared to their partners. [11]

Conversely, an elevated set point of thyroid homeostasis, as quantified by the TT4RI, is associated to higher prevalence of metabolic syndrome [3] and several harmonized criteria by the International Diabetes Federation, including triglyceride and HDL concentration and blood pressure. [12] [13]

In certain phenotypes of non-thyroidal illness syndrome, especially in cases with concomitant sepsis, the TTSI is reduced. [14] This reflects a reduced set point of thyroid homeostasis, as also experimentally predicted in rodent models of inflammation and sepsis. [15] [16] [17]

Negative correlation of the TTSI with the urinary excretion of certain phthalates suggests that endocrine disruptors may affect the central set point of thyroid homeostasis. [18]

See also

References

  1. ↑ Yagi H, Pohlenz J, Hayashi Y, Sakurai A, Refetoff S (1997). "Resistance to thyroid hormone caused by two mutant thyroid hormone receptors beta, R243Q and R243W, with marked impairment of function that cannot be explained by altered in vitro 3,5,3'-triiodothyroinine binding affinity". J. Clin. Endocrinol. Metab. 82 (5): 1608–14. doi: 10.1210/jcem.82.5.3945 . PMID   9141558.
  2. ↑ Pohlenz J, Weiss RE, Macchia PE, Pannain S, Lau IT, Ho H, Refetoff S (1999). "Five new families with resistance to thyroid hormone not caused by mutations in the thyroid hormone receptor beta gene". J. Clin. Endocrinol. Metab. 84 (11): 3919–28. doi: 10.1210/jcem.84.11.6080 . PMID   10566629.
  3. 1 2 Laclaustra, M.; Moreno-Franco, B.; Mateo-Gallego, R.; Perez-Calahorra, S.; Lamiquiz-Moneo, I.; Marco-Benedi, V.; Cenarro, A.; Casasnovas, J.A.; Civeira, F. (August 2018). "Metabolic syndrome prevalence is increased with increasing thyroid hormone resistance levels among normothyroid subjects". Atherosclerosis. 275: e18. doi:10.1016/j.atherosclerosis.2018.06.038. S2CID   81721947.
  4. 1 2 3 Dietrich, JW; Landgrafe-Mende, G; Wiora, E; Chatzitomaris, A; Klein, HH; Midgley, JE; Hoermann, R (2016). "Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research". Frontiers in Endocrinology. 7: 57. doi: 10.3389/fendo.2016.00057 . PMC   4899439 . PMID   27375554.
  5. ↑ Alonso, Manuela; Goodwin, Charles; Liao, XiaoHui; Ortiga-Carvalho, Tania; Machado, Danielle S.; Wondisford, Fredric E.; Refetoff, Samuel; Weiss, Roy E. (August 2009). "Interaction of Steroid Receptor Coactivator (SRC)-1 and the Activation Function-2 Domain of the Thyroid Hormone Receptor (TR) β in TRβ E457A Knock-In and SRC-1 Knockout mice". Endocrinology. 150 (8): 3927–3934. doi:10.1210/en.2009-0093. PMC   2717870 . PMID   19406944.
  6. ↑ Dumitrescu, AM; Refetoff, S; Feingold, KR; Anawalt, B; Boyce, A; Chrousos, G; Dungan, K; Grossman, A; Hershman, JM; Kaltsas, G; Koch, C; Kopp, P; Korbonits, M; McLachlan, R; Morley, JE; New, M; Perreault, L; Purnell, J; Rebar, R; Singer, F; Trence, DL; Vinik, A; Wilson, DP (2000). "Impaired Sensitivity to Thyroid Hormone: Defects of Transport, Metabolism and Action". PMID   25905294.{{cite journal}}: Cite journal requires |journal= (help)
  7. ↑ Ferrara, Alfonso Massimiliano; Onigata, Kazumichi; Ercan, Oya; Woodhead, Helen; Weiss, Roy E.; Refetoff, Samuel (April 2012). "Homozygous Thyroid Hormone Receptor β-Gene Mutations in Resistance to Thyroid Hormone: Three New Cases and Review of the Literature". The Journal of Clinical Endocrinology & Metabolism. 97 (4): 1328–1336. doi:10.1210/jc.2011-2642. PMC   3319181 . PMID   22319036.
  8. ↑ Chatzitomaris, A; Köditz, R; Höppner, W; Peters, S; Klein, HH; Dietrich, JW (12 March 2015). "A novel de novo mutation in the thyroid hormone receptor-beta gene". Experimental and Clinical Endocrinology & Diabetes. 122 (3). doi:10.1055/s-0035-1547617.
  9. ↑ Hoermann, R; Midgley, JEM; Larisch, R; Dietrich, JW (October 2018). "The role of functional thyroid capacity in pituitary thyroid feedback regulation". European Journal of Clinical Investigation. 48 (10) e13003. doi:10.1111/eci.13003. PMID   30022470. S2CID   51698223.
  10. ↑ Panicker, V.; Wilson, S. G.; Spector, T. D.; Brown, S. J.; Falchi, M.; Richards, J. B.; Surdulescu, G. L.; Lim, E. M.; Fletcher, S. J.; Walsh, J. P. (April 2008). "Heritability of serum TSH, free T4 and free T3 concentrations: a study of a large UK twin cohort". Clinical Endocrinology. 68 (4): 652–659. doi:10.1111/j.1365-2265.2007.03079.x. PMID   17970774. S2CID   21809978.
  11. ↑ Jansen, SW; Akintola, AA; Roelfsema, F; van der Spoel, E; Cobbaert, CM; Ballieux, BE; Egri, P; Kvarta-Papp, Z; Gereben, B; Fekete, C; Slagboom, PE; van der Grond, J; Demeneix, BA; Pijl, H; Westendorp, RG; van Heemst, D (19 June 2015). "Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism". Scientific Reports. 5 11525. Bibcode:2015NatSR...511525J. doi:10.1038/srep11525. PMC   4473605 . PMID   26089239.
  12. ↑ Laclaustra, Martin; Moreno-Franco, Belen; Lou-Bonafonte, Jose Manuel; Mateo-Gallego, Rocio; Casasnovas, Jose Antonio; Guallar-Castillon, Pilar; Cenarro, Ana; Civeira, Fernando (February 2019). "Impaired Sensitivity to Thyroid Hormones Is Associated With Diabetes and Metabolic Syndrome". Diabetes Care. 42 (2): 303–310. doi: 10.2337/dc18-1410 . PMID   30552134. S2CID   54632324.
  13. ↑ Guan, Haixia (April 2019). "Mild Acquired Thyroid Hormone Resistance Is Associated with Diabetes-Related Morbidity and Mortality in the General Population". Clinical Thyroidology. 31 (4): 138–140. doi:10.1089/ct.2019;31.138-140. S2CID   145947179.
  14. ↑ Dietrich, J. W.; Ackermann, A.; Kasippillai, A.; Kanthasamy, Y.; Tharmalingam, T.; Urban, A.; Vasileva, S.; Schildhauer, T. A.; Klein, H. H.; Stachon, A.; Hering, S. (19 September 2019). "Adaptive Veränderungen des Schilddrüsenstoffwechsels als Risikoindikatoren bei Traumata". Trauma und Berufskrankheit. 21 (4): 260–267. doi:10.1007/s10039-019-00438-z. S2CID   202673793.
  15. ↑ Kondo, K; Harbuz, MS; Levy, A; Lightman, SL (1997). "Inhibition of the hypothalamic-pituitary-thyroid axis in response to lipopolysaccharide is independent of changes in circulating corticosteroids". Neuroimmunomodulation. 4 (4): 188–94. doi:10.1159/000097337. PMID   9524963.
  16. ↑ Pekary, AE; Stevens, SA; Sattin, A (2007). "Lipopolysaccharide modulation of thyrotropin-releasing hormone (TRH) and TRH-like peptide levels in rat brain and endocrine organs". Journal of Molecular Neuroscience. 31 (3): 245–59. doi:10.1385/jmn:31:03:245. PMID   17726229. S2CID   11463905.
  17. ↑ Fekete, C; Lechan, RM (April 2014). "Central regulation of hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions". Endocrine Reviews. 35 (2): 159–94. doi:10.1210/er.2013-1087. PMC   3963261 . PMID   24423980.
  18. ↑ Chen, Y; Zhang, W; Chen, J; Wang, N; Chen, C; Wang, Y; Wan, H; Chen, B; Lu, Y (2021). "Association of Phthalate Exposure with Thyroid Function and Thyroid Homeostasis Parameters in Type 2 Diabetes". Journal of Diabetes Research. 2021 4027380. doi: 10.1155/2021/4027380 . PMC   8566079 . PMID   34746318.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.