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Synthesis and Regulation of Thyroid Hormones01:20

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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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Natural history of thyroid function in ageing: an individual participant data analysis of 137 488 participants from 31 prospective cohort studies.

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Updated: Sep 15, 2025

Author Spotlight: In Vivo Assessment of Thyroid Hormone Disruption Using the THAI Mouse Model
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Thyroid Hormone Analogs: Recent Developments.

Matthijs E T Freund1, Floor van der Most1, Stefan Groeneweg1,2

  • 1Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands.

Thyroid : Official Journal of the American Thyroid Association
|July 14, 2025
PubMed
Summary
This summary is machine-generated.

Thyroid hormone analogs show promise for treating metabolic dysfunction-associated steatohepatitis and rare genetic disorders. Recent approvals highlight advancements in tissue-specific drug development for enhanced therapeutic outcomes.

Keywords:
MASHMCT8 deficiencyresmetiromthyroid hormone analogstissue specificitytriac

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Area of Science:

  • Endocrinology and Metabolism
  • Pharmacology
  • Genetics

Background:

  • Thyroid hormone receptor (TR) signaling impacts most human tissues, making TRs therapeutic targets.
  • Thyroid hormone analogs are being developed for metabolic disorders and genetic conditions.
  • Recent approvals signify progress in thyroid hormone analog therapeutics since 2020.

Purpose of the Study:

  • To provide an update on developments in thyroid hormone analogs since 2020.
  • To review therapeutic applications in metabolic diseases and genetic disorders.
  • To discuss strategies for enhancing organ specificity.

Main Methods:

  • Review of clinical trials and recent approvals of thyroid hormone analogs.
  • Analysis of therapeutic strategies for metabolic dysfunction-associated steatohepatitis (MASH).
  • Examination of treatments for genetic thyroid hormone signaling disorders like RTHβ and MCT8 deficiency.

Main Results:

  • MGL-3196 (resmetirom) approved for MASH treatment, showing improvements in liver fat, fibrosis, and lipids.
  • VK2809 is under investigation for MASH, designed for liver-specific prodrug conversion.
  • Triac approved for rare RTHβ and MCT8 deficiency, demonstrating efficacy in genetic disorders.

Conclusions:

  • Enhanced organ specificity is crucial, involving TR specificity and tissue-selective activation mechanisms.
  • Recent approvals of two thyroid hormone analogs signal a positive outlook for future development.
  • Targeted strategies promise broader applications of thyroid hormone analogs in medicine.