Thyroid Hormone Mimetics: the Past, Current Status and Future Challenges

Elbers, Laura; Kastelein, John J.P.; Sjouke, Barbara

doi:10.1007/s11883-016-0564-7

Cited by 30 publications

(24 citation statements)

References 51 publications

(61 reference statements)

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“…As they activate, HSCs induce mutual changes in D1 and D3 hepatic expression, especially in D3, which diminishes the active-THs accumulation. These mechanisms can cross-talk in their way to affect TH expression [ 103 ]. Putative evidence is needed to elucidate the exact mechanism behind D1–D3 hepatic repair and the control behind TH homeostasis.…”

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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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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“…Conversely, hyperthyroidism (excess of thyroid hormone), promotes a hypermetabolic state characterized by increased energy expenditure and weight loss [ 40 ]. These beneficial effects of TH have led to the development of selective thyroid hormone mimetics as powerful new tools against atherosclerosis and obesity [ 41 , 42 ]. Moreover, the role of TH has been demonstrated particularly in glucose homeostasis [ 43 ].…”

Section: Effects Of Th On Central Metabolismmentioning

confidence: 99%

Integrating Thyroid Hormone Signaling in Hypothalamic Control of Metabolism: Crosstalk Between Nuclear Receptors

Kouidhi

Clerget-Froidevaux

2018

IJMS

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The obesity epidemic is well recognized as a significant global health issue. A better understanding of the energy homeostasis mechanisms could help to identify promising anti-obesity therapeutic strategies. It is well established that the hypothalamus plays a pivotal role governing energy balance. The hypothalamus consists of tightly interconnected and specialized neurons that permit the sensing and integration of several peripheral inputs, including metabolic and hormonal signals for an appropriate physiological response. Current evidence shows that thyroid hormones (THs) constitute one of the key endocrine factors governing the regulation and the integration of metabolic homeostasis at the hypothalamic level. THs modulate numerous genes involved in the central control of metabolism, as TRH (Thyrotropin-Releasing Hormone) and MC4R (Melanocortin 4 Receptor). THs act through their interaction with thyroid hormone receptors (TRs). Interestingly, TH signaling, especially regarding metabolic regulations, involves TRs crosstalk with other metabolically linked nuclear receptors (NRs) including PPAR (Peroxisome proliferator-activated receptor) and LXR (Liver X receptor). In this review, we will summarize current knowledge on the important role of THs integration of metabolic pathways in the central regulation of metabolism. Particularly, we will shed light on the crosstalk between TRs and other NRs in controlling energy homeostasis. This could be an important track for the development of attractive therapeutic compounds.

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“…However, the thyromimetic eprotirome that has been studied in a phase III clinical trial showed the ability to induce liver injury. 46 Moreover, these drugs likely induce a hypercoagulable state since these drugs specifically stimulate TRβ, and thyroid hormone influences coagulation parameters through this receptor. 47…”

Section: Effects Of Thyroid Hormone On Lipids and The Development Of mentioning

confidence: 99%

Thyroid Disorders and Hemostasis

Elbers

Squizzato

Gerdes

2018

Semin Thromb Hemost

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Lower levels of free thyroxine (whether this is endogenous or exogenous) lead to a hypocoagulable state, and higher levels of free thyroxine lead to a hypercoagulable state. In this narrative review, the effects of different levels of thyroid hormones on clinical end points are described. Hypothyroidism is associated with an increased bleeding risk, whereas hyperthyroidism leads to an increased risk of venous thrombosis. Besides, effects of thyroid hormone on the heart may indirectly influence hemostasis. Hyperthyroidism leads to a higher incidence of atrial fibrillation and atrial flutter, and, at least partly by that mechanism, a higher risk of cerebral arterial thrombosis. In addition, compression effects of goiter on developing venous thrombosis are described. This is caused by local stasis of blood due to tumor expansion.

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Thyroid Hormone Mimetics: the Past, Current Status and Future Challenges

Cited by 30 publications

References 51 publications

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

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

Integrating Thyroid Hormone Signaling in Hypothalamic Control of Metabolism: Crosstalk Between Nuclear Receptors

Thyroid Disorders and Hemostasis

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