Thyroid Biomarkers: Total T3

Optimal Takeaways

Triiodothyronine (T3) is the active form of thyroid hormone in the body. Most circulating T3 is bound to carrier proteins, while a small percentage circulates freely. Measuring total T3 includes both fractions. The thyroid produces only a small amount of T3, while most available T3 is produced in tissues throughout the body. A low serum T3 may be seen with hypothyroidism, iodine or selenium insufficiency, liver or kidney disease, and certain medications. A high total T3 may be seen with hyperthyroidism, hyperproteinemia, pregnancy, inflammation, and certain medications.

Standard Range: 76.00 – 181.00 ng/dL (1.17 – 2.79 nmol/L)        

The ODX Range: 90.00 – 168.00 ng/dL (1.39 – 2.59 nmol/L)

Low total T3 is associated with hypothyroidism, thyroid ablation, iodine insufficiency, myxedema, pituitary or hypothalamic insufficiency, protein depletion and malnutrition, Cushing syndrome, liver disease, and certain drugs, including androgens, anabolic steroids, propranolol, phenytoin, reserpine, and high dose salicylates (Pagana 2021), end-stage renal disease, inflammation (Carrero 2007), euthyroid sick syndrome (Ganesan 2021), caloric deprivation, heart failure, diabetes, kidney disease (Moura 2016), BPA exposure with an increased T4 (Choi 2020), acute stroke, short-term mortality in intensive care, long-term mortality in heart disease (Alevizaki 2007), smoking, alcohol (McGregor 2015), stress, cortisol, lead, cadmium, mercury, free radicals, and oxidative stress (Raymond 2021).

High total T3 is associated with hyperthyroidism, T3 toxicosis, acute thyroiditis, hyperproteinemia, hepatitis, Graves’ disease, Plummer disease, pregnancy, and use of certain drugs, including estrogen, oral contraceptives, and methadone (Pagana 2021). Elevated T3 may be associated with cravings for alcohol (McGregor 2015).

Overview

Triiodothyronine (T3) is the active form of thyroid hormone. It can be measured as total T3 (bound and free) or just free T3, the fraction with the most biological activity. Only 7-10% of thyroid hormone in circulation is T3, and 70% of that is bound to thyroglobulin binding protein, albumin, and prealbumin (Pagana 2021).

Under euthyroid conditions, 80% of circulating T3 is produced from T4 in peripheral tissues, while only 20% is converted in the thyroid gland itself (Abdalla 2014, Chen 2018). In the periphery, deiodination is a primary pathway for converting T4 (four iodine atoms) to T3 (three iodine atoms), a process that requires selenium- Conjugation and lipid peroxidation are additional pathways for the conversion of T4 to T3. Several factors can affect the conversion, including liver and kidney function, nutrition status, and lifestyle factors, including smoking and alcohol intake. Because of the variety of factors that influence T3 status, signs and symptoms of low thyroid function may be due to non-thyroid causes (McGregor 2015). Additional factors that can disrupt 5-deiodinase and T3 production include stress, cortisol, free radicals, oxidative stress, and toxic metals, including mercury, cadmium, and lead (Raymond 2021).

In a prospective study of 210 end-stage renal disease patients, a total T3 of 78.5 ng/dL (1.21 nmol/L) or below was associated with inflammation, endothelial dysfunction, and decreased albumin, hemoglobin, and IGF-1. Researchers note that T3 levels were the best independent predictor of all-cause and cardiovascular mortality in the study group (Carrero 2007).

A low T3 has also been associated with an increased risk of mortality in intensive care patients and in heart disease. Researchers also observed a low T3 following an acute stroke in a study of 737 hospitalized stroke patients. A total T3 of 78 ng/dL (1.2 nmol/L) or below upon admission was associated with significantly decreased independent function and significantly increased risk of mortality 1 year after the initial stroke (Alevizaki 2007).

Significantly lower total T3 and total T4 levels were associated with increased mercury exposure in a study of 137 gold miners. The mean total T3 was 100 ng/mL (1.54 nmol/L) in those exposed to mercury versus 159.74 ng/dL (2.46 nmol/L) in those not exposed (Afrifa 2018).

Mercury can displace selenium, contributing to a functional hypothyroid state. Assessing exposure to heavy metals and other factors, including nutrition status and lifestyle habits, is essential to a comprehensive thyroid assessment.

References

Abdalla, Sherine M, and Antonio C Bianco. “Defending plasma T3 is a biological priority.” Clinical endocrinology vol. 81,5 (2014): 633-41. doi:10.1111/cen.12538

Afrifa, Justice et al. “Variation in thyroid hormone levels is associated with elevated blood mercury levels among artisanal small-scale miners in Ghana.” PloS one vol. 13,8 e0203335. 30 Aug. 2018, doi:10.1371/journal.pone.0203335

Alevizaki, M et al. “Low triiodothyronine: a strong predictor of outcome in acute stroke patients.” European journal of clinical investigation vol. 37,8 (2007): 651-7. doi:10.1111/j.1365-2362.2007.01839.x

Carrero, J J et al. “Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease.” Journal of internal medicine vol. 262,6 (2007): 690-701. doi:10.1111/j.1365-2796.2007.01865.x

Chen, Xinxin et al. “Diagnostic Values of Free Triiodothyronine and Free Thyroxine and the Ratio of Free Triiodothyronine to Free Thyroxine in Thyrotoxicosis.” International journal of endocrinology vol. 2018 4836736. 4 Jun. 2018, doi:10.1155/2018/483673

Choi, Sohyeon et al. “Thyroxine-binding globulin, peripheral deiodinase activity, and thyroid autoantibody status in association of phthalates and phenolic compounds with thyroid hormones in adult population.” Environment international vol. 140 (2020): 105783. doi:10.1016/j.envint.2020.105783

Drutel, Anne, Françoise Archambeaud, and Philippe Caron. "Selenium and the Thyroid Gland." Clin Endocrinol 78.2 (2013): 155-164.

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

McGregor, Brock. "Extra-Thyroidal Factors Impacting Thyroid Hormone Homeostasis." Journal of Restorative Medicine 4.1 (2015): 40-49.

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Raymond, Janice L., et al. Krause and Mahan's Food & the Nutrition Care Process. Elsevier, 2021.