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Reverse T3 (rT3) is the third most abundant form of thyroid hormone in circulation. Levels of rT3 can vary from one tenth those of T3, i.e., 17 ng/dL (0.26 nmol/L) versus 140 ng/dL (2.15 nmol/L) respectively, to an rT3 concentration that is greater than that of T3 (Halsall 2021).
In general, approximately one third of T4 is converted to T3 while one third is converted to rT3 due to variations in the deiodination process. Conversion of T4 to T3 occurs via outer ring deiodination while conversion to rT3 occurs via inner ring deiodination (Peeters 2017).
Reverse T3 is an inactive form of thyroid hormone designed to “put the brakes” on metabolism. Although some rT3 is produced under normal circumstances, production can increase under certain conditions. These include stress, caloric deficit, or critical illness, circumstances associated with non-thyroidal illness syndrome (NTIS), also known as euthyroid sick syndrome. During such times, more T4 can be converted to rT3 with a concomitant decrease in T3 and a decrease in the ratio of T3 to rT3. The shift to reverse T3 may be an adaptive response designed to save energy and protein stores during stress (Moura 2016). Although this metabolic pathway can decrease the catabolism associated with illness, it can become detrimental if prolonged (McGregor 2015).
One study investigated central hypothyroidism versus euthyroid sick syndrome/NTIS in 78 subjects with low free T4 and low/normal TSH, and 35 healthy controls. Results indicate that a low mean rT3 level of 8.78 ng/dL (0.14 nmol/L) was associated with central hypothyroidism and did not normalize until T4 was administered. However, the elevated mean rT3 of 23.81 ng/dL (0.37 nmol/L) seen with NTIS resolved over time along with other thyroid biomarkers (Exley 2021).
DeGroot, Leslie J. “The Non-Thyroidal Illness Syndrome.” Endotext, edited by Kenneth R Feingold et. al., MDText.com, Inc., 1 February 2015.
Exley, Sarah, Sonal Banzal, and Udaya Kabadi. "Low Reverse T3: A Reliable, Sensitive and Specific in Diagnosis of Central Hypothyroidism." Open Journal of Endocrine and Metabolic Diseases 11.7 (2021): 137-143.
Halsall, David J, and Susan Oddy. “Clinical and laboratory aspects of 3,3',5'-triiodothyronine (reverse T3).” Annals of clinical biochemistry vol. 58,1 (2021): 29-37. doi:10.1177/0004563220969150
McGregor, Brock. "Extra-Thyroidal Factors Impacting Thyroid Hormone Homeostasis." Journal of Restorative Medicine 4.1 (2015): 40-49.
Moura Neto, Arnaldo, and Denise Engelbrecht Zantut-Wittmann. “Abnormalities of Thyroid Hormone Metabolism during Systemic Illness: The Low T3 Syndrome in Different Clinical Settings.” International journal of endocrinology vol. 2016 (2016): 2157583. doi:10.1155/2016/2157583
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Peeters, Robin P, and Theo J Visser. “Metabolism of Thyroid Hormone.” Endotext, edited by Kenneth R Feingold et. al., MDText.com, Inc., 1 January 2017.
Sathyapalan, Thozhukat et al. “The Effect of High Dose Isoflavone Supplementation on Serum Reverse T3 in Euthyroid Men With Type 2 Diabetes and Post-menopausal Women.” Frontiers in endocrinology vol. 9 698. 22 Nov. 2018, doi:10.3389/fendo.2018.00698
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Wilson, Julian Bryant, and Theodore C. Friedman. "Reverse T3 in Patients With Hypothyroidism, Helpful or a Waste of Time?." Journal of the Endocrine Society 5.Supplement_1 (2021): A952-A952.