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 Screening may refer to: * Screening cultures, a type a medical test that is done to find an infection * Screening (economics), a strategy of combating adverse selection (includes sorting resumes to select employees) * Screening (environmental), a ...

for resistance to thyroid hormone. Today it is also used to get an estimate for the set point of thyroid homeostasis, especially to assess dynamic thyrotropic adaptation of the anterior pituitary gland, including non-thyroidal illnesses.

How to determine TTSI

Universal form

The TTSI can be calculated with :

TTSI =

from equilibrium

serum Serum may refer to: *Serum (blood), plasma from which the clotting proteins have been removed **Antiserum, blood serum with specific antibodies for passive immunity * Serous fluid, any clear bodily fluid * Truth serum, a drug that is likely to mak ...

plasma Plasma or plasm may refer to: Science * Plasma (physics), one of the four fundamental states of matter * Plasma (mineral), a green translucent silica mineral * Quark–gluon plasma, a state of matter in quantum chromodynamics Biology * Blood pla ...

concentrations of thyrotropin (TSH), free T4 (FT4) and the

assay An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity of a ...

-specific upper limit of the

reference interval In medicine and health-related fields, a reference range or reference interval is the range (statistics), range or the interval (mathematics), interval of values that is deemed normal for a physiology, physiological measurement in healthy persons ...

for FT4 concentration (''l_u'').

Reference ranges

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 :

TTSI =

. The disadvantage of this uncorrected version is that its numeric results are highly dependent on the used

s and their units of measurement.

Biochemical associations

In case of resistance to thyroid hormone, the magnitude of TTSI depends on which nucleotide in the

THRB Thyroid hormone receptor beta (TR-beta) also known as nuclear receptor subfamily 1, group A, member 2 (NR1A2), is a nuclear receptor protein that in humans is encoded by the ''THRB'' gene. Function The protein encoded by this gene is a nuclear ...

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 The nuclear receptor coactivator 1 (''NCOA1'') is a transcriptional coregulatory protein that contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity. NCOA1 is recruited to DNA promotion sites by l ...

) gene.

Clinical significance

The TTSI is used as a screening parameter for resistance to thyroid hormone due to mutations in the

gene, where it is elevated. It is also beneficial for assessing the severity of already confirmed thyroid hormone resistance, even on replacement therapy with L-T4, and for monitoring the pituitary response to substitution therapy with thyromimetics (e.g. TRIAC) in RTH Beta. In

autoimmune thyroiditis Autoimmune thyroiditis, is a chronic disease in which the body interprets the thyroid glands and its hormone products T3, T4 and TSH as threats, therefore producing special antibodies that target the thyroid's cells, thereby destroying it. It ma ...

the TTSI is moderately elevated. A large cohort study demonstrated TTSI to be strongly influenced by genetic factors. 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. Conversely, an elevated set point of thyroid homeostasis, as quantified by the TT4RI, is associated to higher prevalence of

metabolic syndrome Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Metabolic syndrome ...

and several harmonized criteria by the International Diabetes Federation, including triglyceride and HDL concentration and

blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...

. In certain phenotypes of

non-thyroidal illness syndrome Euthyroid sick syndrome (ESS) is a state of adaptation or dysregulation of thyrotropic feedback control wherein the levels of T3 and/or T4 are abnormal, but the thyroid gland does not appear to be dysfunctional. This condition may result from ...

, especially in cases with concomitant sepsis, the TTSI is reduced. This reflects a reduced set point of thyroid homeostasis, as also experimentally predicted in rodent models of inflammation and sepsis. Negative correlation of the TTSI with the urinary excretion of certain phthalates suggests that

endocrine disruptor Endocrine disruptors, sometimes also referred to as hormonally active agents, endocrine disrupting chemicals, or endocrine disrupting compounds are chemicals that can interfere with endocrine (or hormonal) systems. These disruptions can cause c ...

s may affect the central set point of thyroid homeostasis.

References

{{Reflist, 2 Chemical pathology Blood tests Endocrine procedures Thyroidological methods Thyroid homeostasis Structure parameters of thyroid function Static endocrine function tests