Reverse T3, Serum

Additional Information:

UFHPL Epic order code: LAB138

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

Footnotes

  1. Economidou F, Douka E, Tzanela M, Nanas S, Kotanidou A. Thyroid function during critical illness. Hormones (Athens). 2011 Apr-Jun; 10(2):117-124. PubMed 21724536
  2. Warner MH, Beckett GJ. Mechanisms behind the non-thyroidal illness syndrome: An update. J Endocrinol. 2010 Apr; 205(1):1-13. PubMed 20016054
  3. Forestier E, Vinzio S, Sapin R, Schlienger JL, Goichot B. Increased reverse triiodothyronine is associated with shorter survival in independently-living elderly: The ALSANUT study. Eur J Endocrinol. 2009 Feb; 160(2):207-214. PubMed 19001060
  4. Peeters RP, van der Geyten S, Wouters PJ, et al. Tissue thyroid hormone levels in critical illness. J Clin Endocrinol Metab. 2005 Dec; 90(12):6498-6507. PubMed 16174716
  5. Peeters RP, Wouters PJ, van Toor H, Kaptein E, Visser TJ, Van den Berghe G. Serum 3,3′,5′-triiodothyronine (rT3) and 3,5,3'-triiodothyronine/rT3 are prognostic markers in critically ill patients and are associated with postmortem tissue deiodinase activities. J Clin Endocrinol Metab. 2005 Aug; 90(8):4559-4565. PubMed 15886232
  6. Friberg L, Drvota V, Bjelak AH, Eggertsen G, Ahnve S. Association between increased levels of reverse triiodothyronine and mortality after acute myocardial infarction. Am J Med. 2001 Dec 15; 111(9):699-703. PubMed 11747849
  7. Friberg L, Werner S, Eggertsen G, Ahnve S. Rapid down-regulation of thyroid hormones in acute myocardial infarction: Is it cardioprotective in patients with angina? Arch Intern Med. 2002 Jun 24; 162(12):1388-1394. PubMed 12076238
  8. Pimentel CR, Miano FA, Perone D, et al. Reverse T3 as a parameter of myocardial function impairment in heart failure. Int J Cardiol. 2010 Nov 5; 145(1):52-53. PubMed 19428128
  9. Goichot B, Schlienger JL, Grunenberger F, Pradignac A, Sapin R. Thyroid hormone status and nutrient intake In the free-living elderly. Interest of reverse triiodothyronine assessment. Eur J Endocrinol. 1994 Mar; 130(3):244-252. PubMed 8156097
  10. van den Beld AW, Visser TJ, Feelders RA, Grobbee DE, Lamberts SW. Thyroid hormone concentrations, disease, physical function, and mortality in elderly men. J Clin Endocrinol Metab. 2005 Dec; 90(12):6403-6409. PubMed 16174720

CPT Code(s):

84482

Specimen Requirements:

Type: Serum
Container/Tube: Red-top tube or gel-barrier tube

  • If a red-top tube is used, transfer the separated serum to a plastic transport tube.

Sample Volume: 0.8 mL

Minimum Volume: 0.3 mL (Repeat testing is not possible with this specimen volume.)

Storage: Refrigerate specimens after collection.

Stability (collection to time of analysis/testing):

  • Ambient: 14 days
  • Refrigerated: 14 days
  • Frozen: 14 days
  • Freeze/Thaw cycles: Stable (x3)
Rejection Criteria:

  • Citrate plasma specimen
  • Improper labeling

Methodology:

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

Reference Values:

Reference Intervals

Age

Range (ng/dL)

Premature (26 to 31 weeks old)

33.0 − 147.0

Premature (32 to 35 weeks old)

49.0 − 217.0

Full-term ( 2 to 7 days old)

33.0 − 206.0

8 days to 5 months old

13.0 − 107.0

6 to 12 months old

8.1 − 52.8

1 to 15 yyears old

8.3 − 22.9

16 years and older

9.2 − 24.1

Performed:

Monday - Friday