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T3 levels and thyroid hormone signaling

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Salas-Lucia, Federico, Bianco, Antonio C.·2022·Frontiers in Endocrinology
DOI 10.3389/fendo.2022.1044691PMC PMC9646642
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Abstract

The clinical availability of tissue-specific biomarkers of thyroid hormone (TH) action constitutes a “holy grail” for the field. Scientists have investigated several TH-dependent markers, including the tissue content of triiodothyronine (T3)—the active form of TH. The study of animal models and humans indicates that the T3 content varies among different tissues, mostly due to the presence of low-affinity, high-capacity cytoplasmic T3 binding proteins. Nonetheless, given that T3 levels in the plasma and tissues are in equilibrium, T3 signaling is defined by the intracellular free T3 levels. The available techniques to assess tissue T3 are invasive and not clinically applicable. However, the tracer kinetic studies revealed that serum T3 levels can accurately predict tissue T3 content and T3 signaling in most tissues, except for the brain and pituitary gland. This is true not only for normal individuals but also for patients with hypo or hyperthyroidism–but not for patients with non-thyroidal illness syndrome. Given this direct relationship between serum and tissue T3 contents and T3 signaling in most tissues, clinicians managing patients with hypothyroidism could refocus attention on monitoring serum T3 levels. Future clinical trials should aim at correlating clinical outcomes with serum T3 levels.

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Authors
Salas-Lucia, F., & Bianco, A. C.
Affiliations
University of Chicago (US)
Corresponding author
Salas-Lucia, Federico
ORCID
Venue
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Published
2022-10-27
Volume
13
Pages
1044691-1044691
ISSN
1664-2392 (ISSN-L)
DOI
10.3389/fendo.2022.1044691
PMC
PMC9646642
OpenAlex
W4307799310
Cited by
66
References
20
Citations by year
2026: 13 · 2025: 20 · 2024: 16 · 2023: 17
FWCI
1.89
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journal article
Language
en
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  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
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  • University of Chicago (cc-by)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058538, R01DK065055, R01DK015070)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
triiodothyronine, thyroid hormone signaling, hypothyroidism, hyperthyroidism, low T3 syndrome, thyroid function monitoring
MeSH terms
Animals, Humans, Hypothyroidism, Kinetics, Thyroid Function Tests, Thyroid Hormones, Thyroxine, Triiodothyronine

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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