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Background
Triiodothyronine (T3) is the physiologically active thyroid hormone (TH), so fluctuations in tissue levels of T3 may reflect the role of T3 in any given tissue, all else being equal. A better understanding of changes in tissue T3 content can assist clinicians in understanding the disease state of their patients. Examples include the recovery of TH and T3 function during the treatment of hypothyroid patients, and how the role of TH is affected in patients who restrict their caloric intake or have non-thyroidal illness syndrome (NTIS). However, existing techniques for studying tissue T3 levels are usually invasive and have little clinical applicability, so T3 effects are generally inferred from serum T3 levels.
Figure 1. TRH-TSH-T3 feedback loop (Source: Kim HY, et al. 2013)
Improvements in the sensitivity and specificity of thyroid testing have led to the detection and treatment of thyroid disease. Initially thyroid function was assessed by basal metabolic rate and bioassays, but later laboratory tests were added to clinical thyroid diagnosis, mainly by measuring TH by measuring protein-bound iodine, a method that indirectly estimates total T4 (TT4) concentration. Because abnormal TH-binding proteins can interfere with TH measurement and make TT4 assessment inaccurate, indirect TBG assessment methods were subsequently developed to provide indirect estimates of free T4. Current assays using TH-binding ratios use primarily autoimmune preparations and non-isotopic signals to assess available TBG-binding sites relative to a "normal" reference value. Depending on the method, the reference value may be set at 1.00 or 40%.
99.7% of T3 is bound to proteins, and direct measurement of free T3 (fT3) is theoretically a better indicator of thyroid function than total T3 (TT3). However, T3 is less concentrated in the circulation than T4 and has a weaker binding affinity for carrier proteins in serum than T4. fT3 measurements are more susceptible to interference from free fatty acids and drugs in the circulation. As a result, fT3 immunoassays are less accurate and reproducible than fT4. In clinical applications, T3 concentrations in patients with hypothyroidism are generally maintained within the reference interval, so T3 testing in patients with suspected hypothyroidism or elevated thyrotropin is of limited clinical value. Circulating T3 is elevated before T4 in patients with hyperthyroidism, so T3 analysis may provide clinically relevant information in patients with suppressed TSH. Deiodinase activity in patients with NTIS may be altered with the disease, resulting in a conversion of T4 to T3, a condition that may cause patients to develop low T3 concentrations.
Alternative Names
Anti-T3 monoclonal antibody
References
1. Van Uytfanghe K, et al. Thyroid Stimulating Hormone and Thyroid Hormones (Triiodothyronine and Thyroxine): An American Thyroid Association-Commissioned Review of Current Clinical and Laboratory Status. Thyroid. 2023 Sep;33(9):1013-1028.
2. Morris JC, et al. The isolation of thyroxine (T4), the discovery of 3,5,3'-triiodothyronine (T3), and the identification of the deiodinases that generate T3 from T4: An historical review. Endocrine. 2019 Oct;66(1):3-9.
3. Kim HY, et al. Role and Mechanisms of Actions of Thyroid Hormone on the Skeletal Development. Bone Res. 2013 Jun 28;1(2):146-61.
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References
Effects of Triiodothyronine Treatment in an Animal Model of Heart Failure with Preserved Ejection Fraction
Thyroid
Authors: Neves JS, Leite AR, Conceição G, Gonçalves A, Borges-Canha M, Vale C, Von-Hafe M, Martins D, Miranda-Silva D, Leite S, Rocha-Oliveira E, Sousa-Mendes C, Chaves J, Lourenço IM, Grijota-Martínez C, Bárez-López S, Miranda IM, Almeida-Coelho J, Vasques-Nóvoa F, Carvalho D, Lourenço A, Falcão-Pires I, Leite-Moreira A.
Background: Low levels of triiodothyronine (T3) are common in patients with heart failure (HF). Our aim was to evaluate the effects of supplementation with low and replacement doses of T3 in an animal model of HF with preserved ejection fraction (HFpEF). Methods: We evaluated four groups: ZSF1 Lean (n = 8, Lean-Ctrl), ZSF1 Obese (rat model of metabolic-induced HFpEF, n = 13, HFpEF), ZSF1 Obese treated with a replacement dose of T3 (n = 8, HFpEF-T3high), and ZSF1 Obese treated with a low-dose of T3 (n = 8, HFpEF-T3low). T3 was administered in drinking water from weeks 13 to 24. The animals underwent anthropometric and metabolic assessments, echocardiography, and peak effort testing with maximum O2 consumption (VO2max) determination at 22 weeks, and a terminal hemodynamic evaluation at 24 weeks. Afterwhile myocardial samples were collected for single cardiomyocyte evaluation and molecular studies. Results: HFpEF animals showed lower serum and myocardial thyroid hormone levels than Lean-Ctrl. Treatment with T3 did not normalize serum T3 levels, but increased myocardial T3 levels to normal levels in the HFpEF-T3high group. Body weight was significantly decreased in both the T3-treated groups, comparing with HFpEF. An improvement in glucose metabolism was observed only in HFpEF-T3high. Both the treated groups had improved diastolic and systolic function in vivo, as well as improved Ca2+ transients and sarcomere shortening and relaxation in vitro. Comparing with HFpEF animals, HFpEF-T3high had increased heart rate and a higher rate of premature ventricular contractions. Animals treated with T3 had higher myocardial expression of calcium transporter ryanodine receptor 2 (RYR2) and α-myosin heavy chain (MHC), with a lower expression of β-MHC. VO2max was not influenced by treatment with T3. Myocardial fibrosis was reduced in both the treated groups. Three animals died in the HFpEF-T3high group. Conclusions: Treatment with T3 was shown to improve metabolic profile, myocardial calcium handling, and cardiac function. While the low dose was well-tolerated and safe, the replacement dose was associated with increased heart rate, and increased risk of arrhythmias and sudden death. Modulation of thyroid hormones may be a potential therapeutic target in HFpEF; however, it is important to take into account the narrow therapeutic window of T3 in this condition.
Povidone-iodine-induced transient triiodothyronine thyrotoxicosis in a Japanese patient with prolonged habitual gargling: A case report and literature review
Rationale: Iodine-induced hyperthyroidism and triiodothyronine (T3) thyrotoxicosis in patients who routinely gargle with povidone-iodine (PVP-I) gargling solution are rare in Japan.
Patient concerns: A 50-year-old man presented to our hospital for a close examination of an enlarged thyroid, which was noted during a complete health checkup. The thyroid was slightly enlarged with no palpable nodules. He had an increased appetite but no weight gain. He had been routinely gargling with PVP-I gargling solution 4 times daily for >10 years. He had no history of thyroid disease.
Diagnoses: Test results revealed suppressed thyroid-stimulating hormone, normal free thyroxine, and increased free triiodothyronine levels, leading to the diagnosis of T3 thyrotoxicosis.
Interventions: The patient agreed to stop gargling with PVP-I gargle solution.
Outcomes: The free triiodothyronine and thyroid-stimulating hormone levels returned to normal at 18 and 21 weeks, respectively, after discontinuation of PVP-I gargling. After an improvement in thyroid function, he gained 5 kg in 1 year.
Lessons: To our knowledge, this is the first case report that describes PVP-I gargle-induced T3 thyrotoxicosis in a healthy individual without thyroid disease. In Japan, which is an iodine-sufficient country, considering the possibility of high-dose iodine intake-induced thyrotoxicosis due to long-term PVP-I gargling or other causes is necessary, even in individuals with no history of thyroid disease.