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Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
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The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
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Thyroid Hormone Mimetics: the Past, Current Status and Future Challenges.

L P B Elbers1,2, J J P Kastelein1, B Sjouke3

  • 1Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

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Thyroid hormone mimetics show promise for lowering low-density lipoprotein cholesterol but face challenges. Developing selective thyromimetics without side effects remains a key hurdle for treating dyslipidemia.

Keywords:
DyslipidemiaLow-density lipoprotein cholesterolThyroid hormone mimeticsThyroid hormone receptor

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Area of Science:

  • Endocrinology
  • Pharmacology
  • Cardiovascular Medicine

Background:

  • Thyroid hormone levels influence low-density lipoprotein cholesterol (LDL-C).
  • Thyroid hormone mimetics are being explored as potential lipid-lowering agents.
  • Selective targeting of thyroid hormone receptors (TRα and TRβ) is crucial.

Purpose of the Study:

  • To review the literature on thyromimetics for dyslipidemia treatment.
  • To analyze the development, efficacy, and safety of these agents.
  • To identify challenges in creating novel, effective thyromimetics.

Main Methods:

  • Literature review of preclinical and clinical studies on thyromimetics.
  • Analysis of drug development pathways and clinical trial outcomes.
  • Evaluation of receptor selectivity and organ specificity.

Main Results:

  • Several thyromimetics have been investigated for lowering LDL-C.
  • No thyromimetic has successfully completed Phase III clinical trials without adverse effects.
  • Improvements in receptor selectivity and organ specificity have been achieved.

Conclusions:

  • Thyroid hormone mimetics offer a potential therapeutic strategy for dyslipidemia.
  • Significant challenges remain in developing safe and effective thyromimetic drugs.
  • Future research should focus on overcoming safety concerns and improving therapeutic outcomes.