Reverse T3, Serum

Test ID: 


CPT code:



T3, Reverse

Test Information:

Reverse triiodothyronine (rT3) is an isomer of triiodothyronine (T3) with no demonstrated biological activity. The majority of rT3is produced through peripheral enzymatic monodeiodination of T4 at the 5 position of the inner ring of the iodothyronine nucleus of thyroxine (T4). A lesser amount of rT3 is secreted directly by the thyroid gland. Reverse T3 is biologically inactive and does not stimulate thyroid hormone receptors.  Multiple changes in serum thyroid hormone levels are commonly observed secondary to acute (eg, septic shock, myocardial infarction) or chronic (eg, cancer, advanced acquired immunodeficiency syndrome) systemic nonthyroidal illnesses. The hallmark features of this “nonthyroidal illness syndrome” are a low serum T3 level accompanied by an increase in serum rT3 level. Diminished serum T3 levels (the most biologically-active thyroid hormone) are thought to reflect altered thyroid homeostasis as a mechanism of adapting to severe illness. “Low T3 syndrome” affects the majority of critically ill patients and many outpatients suffering less acute illness. Thyroid-stimulating hormone (TSH), thyroxine (T4), free T4 (FT4), and free T4 index (FTI) can also be affected to variable degrees depending on the severity and duration of the illness. This constellation of abnormal thyroid hormone levels has historically been referred to as the euthyroid sick syndrome (ESS), because these patients are considered to be clinically euthyroid and typically have no hypothalamic, pituitary, or thyroid gland dysfunction, and thyroid hormone levels generally normalize on resolution of the underlying illness.  The conversion of T4 to rT3 is increased in ESS in large part because of increased 5′-deiodinase activity in the periphery.  This is often referred to as the “thyroid hormone inactivating pathway” because it reduces the amount of T4 available for conversion to biologically active T3.  Also, the conversion of rT3 to diiodothyronine (T2) is reduced in nonthyroidal illness because of inhibition of the 5′-monodeiodinase activity.   A number of studies have revealed that the expression of these deiodinases is modified by illness in a highly organ-specific manner resulting in tissue-specific modifications to thyroid status.  In acutely ill patients (after acute myocardial infarction or other patients in intensive care), an elevated rT3 level has been found to independently predict increased mortality.  Significant changes in rT3 occur rapidly in acute illness with maximal changes 24 to 36 hours after the onset of symptoms.  Reverse T3 increase also appears to correlate with the degree of myocardial function impairment in patients with heart failure.  Reverse T3 is often increased in nonacutely ill elderly people.   The Alsanut study, an epidemiological study conducted in the late 1980s, was designed to determine the prevalence of thyroid dysfunction in an independently living population of 440 elderly individuals.  This study revealed a significant relationship between increased rT3 and shorter survival while taking into consideration other critical confounders such as age, gender, medical history, nutritional parameters, and energy intake. In this study, rT3 was the only thyroid hormone associated with shorter survival.  Van den Beld found that elderly persons with isolated increased rT3 had lower physical performance and that elevated rT3 may be associated with a poor global health status.  Forestier found a strong association between rT3 and survival in a population of independently living elderly subjects regardless of other confounding factors.

Specimen Type:


Requested Volume: 

1 mL

Minimum Volume: 

0.6 mL (Note: This volume does not allow for repeat testing.)

Container Type: 

Red-top tube or gel-barrier tube


If a tube other than a gel-barrier tube is used, transfer separated serum to a plastic transport tube.

Storage Instructions:

Room temperature

Stability Requirements:



Room temperature

14 days


14 days


14 days

Freeze/thaw cycles

Stable x3


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MCI Diagnostic

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