We All Know We Need Them, We Hope They Are Coming, But When?

Bianco, Antonio C.

doi:10.1089/thy.2020.0250

Cited by 3 publications

(2 citation statements)

References 14 publications

(18 reference statements)

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“…Having clinically relevant tissue-specific biomarkers that reflect T3 action is the ultimate goal of clinical scientists that study TH action (51). For example, serum TSH, is the best biomarker for T3 action in the medial-basal hypothalamus and pituitary gland, reflecting the plasma levels of both T4 and T3.…”

Section: Changes In Tissue T3 Content In Disease Statesmentioning

confidence: 99%

T3 levels and thyroid hormone signaling

Salas-Lucia

Bianco

2022

Front. Endocrinol.

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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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Section: Changes In Tissue T3 Content In Disease Statesmentioning

confidence: 99%

T3 levels and thyroid hormone signaling

Salas-Lucia

Bianco

2022

Front. Endocrinol.

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“…The thyroid gland is a pivotal endocrine organ responsible for thermogenesis, adipogenesis, fat distribution, energy, lipid, protein, carbohydrate, and cell metabolism [ 80 ]. The THs 3,5,3′-triiodothyronine (T3) and 3,5,3′,5′-tetraiodothyronine/thyroxine (T4) are important keys for tissue repair as they mediate cellular differentiation and interfere with cell-signaling mechanisms via protein–protein synergy through collaboration with nuclear receptors or binding to other proteins [ 81 , 82 ]. Production of THs from the thyroid gland is modulated centrally by thyrotrophs of the anterior pituitary that produce TSH, which in turn is regulated by the hypothalamus.…”

Section: Immunopathogenesismentioning

confidence: 99%

Hypothyroidism-Induced Nonalcoholic Fatty Liver Disease (HIN): Mechanisms and Emerging Therapeutic Options

Gosav

Neculae

Costea

et al. 2020

IJMS

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Nonalcoholic fatty liver disease (NAFLD) is an emerging worldwide problem and its association with other metabolic pathologies has been one of the main research topics in the last decade. The aim of this review article is to provide an up-to-date correlation between hypothyroidism and NAFLD. We followed evidence regarding epidemiological impact, immunopathogenesis, thyroid hormone-liver axis, lipid and cholesterol metabolism, insulin resistance, oxidative stress, and inflammation. After evaluating the influence of thyroid hormone imbalance on liver structure and function, the latest studies have focused on developing new therapeutic strategies. Thyroid hormones (THs) along with their metabolites and thyroid hormone receptor β (THR-β) agonist are the main therapeutic targets. Other liver specific analogs and alternative treatments have been tested in the last few years as potential NAFLD therapy. Finally, we concluded that further research is necessary as well as the need for an extensive evaluation of thyroid function in NAFLD/NASH patients, aiming for better management and outcome.

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Novel Biomarkers Reveal Mismatch Between Tissue and Serum Thyroid Hormone Status in Amiodarone-Induced Hyperthyroidism

Sinkó,

Katkó,

Tóth

et al. 2024

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Serum TSH and thyroid hormone (TH) levels are routine markers of thyroid function. However, their diagnostic performance is limited under special conditions, e.g. in amiodarone-induced hyperthyroidism (AIH). Such cases would require the assessment of tissue TH action, which is currently unfeasible. Objective Development of an approach that determines how well serum parameters are reflected in tissue TH action of patients. Methods TH-responsive marker genes were identified from human hair follicles (HF) with Next Generation Sequencing, validated by qPCR. A classification model was built with these markers to assess tissue TH action and was deployed on amiodarone treated patients. The impact of amiodarone on tissue TH action was also studied in Thyroid Hormone Action Indicator (THAI) mice. Results The classification model was validated and shown to predict tissue TH status of subjects with good performance. Serum- and HF-based TH statuses were concordant in hypothyroid and euthyroid amiodarone treated patients. In contrast, amiodarone decreased the coincidence of serum-based and HF-based TH statuses in hyperthyroid patients, indicating that AIH is not unequivocally associated with tissue hyperthyroidism. This was confirmed in the THAI model, where amiodarone prevented tissue hyperthyroidism in THAI mice despite high serum fT4. Conclusion We developed a minimally-invasive approach using HF markers to assess tissue TH economy that could complement routine diagnostics in controversial cases. We observed that a substantial proportion of AIH patients do not develop tissue hyperthyroidism, indicating that amiodarone protects tissues from thyrotoxicosis. Assessing tissue TH action in patients with AIH may be warranted for treatment decisions.

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We All Know We Need Them, We Hope They Are Coming, But When?

Cited by 3 publications

References 14 publications

T3 levels and thyroid hormone signaling

T3 levels and thyroid hormone signaling

Hypothyroidism-Induced Nonalcoholic Fatty Liver Disease (HIN): Mechanisms and Emerging Therapeutic Options

Novel Biomarkers Reveal Mismatch Between Tissue and Serum Thyroid Hormone Status in Amiodarone-Induced Hyperthyroidism

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