Chemistry:Thyrotroph Thyroid Hormone Sensitivity Index
Thyrotroph Thyroid Hormone Sensitivity Index | |
---|---|
Medical diagnostics | |
Synonyms | TTSI, Thyrotroph T4 Resistance Index, TT4RI |
Reference range | 100-150 |
Test of | Sensitivity 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]
How to determine TTSI
Universal form
The TTSI can be calculated with
- [math]\displaystyle{ TTSI = {100 \cdot TSH \cdot FT4 \over l_u} }[/math]
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
Parameter | Lower limit | Upper limit | Unit |
TTSI | 100 | 150 |
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
- [math]\displaystyle{ TTSI = {100 \cdot TSH \cdot FT4} }[/math].
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
- Thyroid function tests
- Thyroid's secretory capacity
- Sum activity of peripheral deiodinases
- Jostel's TSH index
- Thyroid Feedback Quantile-based Index
References
- ↑ "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. 1997. doi:10.1210/jcem.82.5.3945. PMID 9141558.
- ↑ "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. 1999. doi:10.1210/jcem.84.11.6080. PMID 10566629.
- ↑ 3.0 3.1 Laclaustra, M.; Moreno-Franco, B.; Mateo-Gallego, R.; Perez-Calahorra, S.; Lamiquiz-Moneo, I.; Marco-Benedi, V.; Cenarro, A.; Casasnovas, J.A. et al. (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.
- ↑ 4.0 4.1 4.2 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. PMID 27375554.
- ↑ 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. PMID 19406944.
- ↑ Dumitrescu, AM; Refetoff, S; Feingold, KR; Anawalt, B; Boyce, A; Chrousos, G; Dungan, K; Grossman, A et al. (2000). Impaired Sensitivity to Thyroid Hormone: Defects of Transport, Metabolism and Action. PMID 25905294.
- ↑ 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. PMID 22319036.
- ↑ 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.
- ↑ 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.
- ↑ Panicker, V.; Wilson, S. G.; Spector, T. D.; Brown, S. J.; Falchi, M.; Richards, J. B.; Surdulescu, G. L.; Lim, E. M. et al. (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.
- ↑ Jansen, SW; Akintola, AA; Roelfsema, F; van der Spoel, E; Cobbaert, CM; Ballieux, BE; Egri, P; Kvarta-Papp, Z et al. (19 June 2015). "Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism.". Scientific Reports 5: 11525. doi:10.1038/srep11525. PMID 26089239. Bibcode: 2015NatSR...511525J.
- ↑ 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.
- ↑ 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.
- ↑ Dietrich, J. W.; Ackermann, A.; Kasippillai, A.; Kanthasamy, Y.; Tharmalingam, T.; Urban, A.; Vasileva, S.; Schildhauer, T. A. et al. (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.
- ↑ 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.
- ↑ 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.
- ↑ 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. PMID 24423980.
- ↑ Chen, Y; Zhang, W; Chen, J; Wang, N; Chen, C; Wang, Y; Wan, H; Chen, B et al. (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. PMID 34746318.
Original source: https://en.wikipedia.org/wiki/Thyrotroph Thyroid Hormone Sensitivity Index.
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