Thyrotroph Thyroid Hormone Sensitivity Index
Thyrotroph Thyroid Hormone Sensitivity Index | |
---|---|
Reference range | 100-150 |
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
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
Parameter | Lower limit | Upper limit | Unit |
TTSI | 100 | 150 |
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[5], even on replacement therapy with L-T4[6], and for monitoring the pituitary response to substitution therapy with thyromimetics (e.g. TRIAC) in RTH Beta.[7]
In autoimmune thyroiditis the TTSI is moderately elevated.[8]
A large cohort study demonstrated TTSI to be strongly influenced by genetic factors.[9] 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.[10]
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[11].
See also
- Thyroid function tests
- Thyroid's secretory capacity
- Sum activity of peripheral deiodinases
- Jostel's TSH index
References
- ^ 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.
- ^ 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.
- ^ a b 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.
- ^ a b c 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.
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: CS1 maint: unflagged free DOI (link) - ^ 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.
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(help) - ^ 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.; 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.
- ^ 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. doi:10.1038/srep11525. PMC 4473605. PMID 26089239.
- ^ 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.