Reverse T₃

Serum

1.2 mL

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

Red-top tube or gel-barrier tube

This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration.

Liquid chromatography/tandem mass spectrometry (LC/MS-MS)

See table.

Reverse triiodothyronine (rT₃) is an isomer of triiodothyronine (T₃) with no demonstrated biological activity.^1,2 The majority of rT₃ is 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.^1-3 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.¹ "Low T₃ syndrome" affects the majority of critically ill patients and many outpatients suffering less acute illness.^1,2 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.^1-3 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.^1,2

The conversion of T₄ to rT₃ is increased in ESS in large part because of increased 5'-deiodinase activity in the periphery.^1,2 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.^1,2 Also, the conversion of rT₃ to diiodothyronine (T₂) is reduced in nonthyroidal illness because of inhibition of the 5'-monodeiodinase activity.¹ 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.²

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.^4-8 Significant changes in rT₃ occur rapidly in acute illness with maximal changes 24 to 36 hours after the onset of symptoms.^6,7 Reverse T₃ increase also appears to correlate with the degree of myocardial function impairment in patients with heart failure.⁸

Reverse T₃ is often increased in nonacutely ill elderly people.^3,9,10 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.⁹ 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.⁹ 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.¹⁰ Forestier found a strong association between rT₃ and survival in a population of independently living elderly subjects regardless of other confounding factors.³