Thyrotroph Thyroid Hormone Sensitivity Index
Thyrotroph Thyroid Hormone Sensitivity Index | |
---|---|
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[edit | edit source]
Universal form[edit | edit source]
The TTSI can be calculated with
- <math>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[edit | edit source]
Parameter | Lower limit | Upper limit | Unit |
TTSI | 100 | 150 |
Short form[edit | edit source]
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>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.
Biochemical associations[edit | edit source]
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[edit | edit source]
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].
See also[edit | edit source]
- Thyroid function tests
- Thyroid's secretory capacity
- Sum activity of peripheral deiodinases
- Jostel's TSH index
References[edit | edit source]
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