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Updated: Sep 24, 2025

Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
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Glucocorticoid receptor blockers.

Mark E Molitch1

  • 1Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. molitch@northwestern.edu.

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|May 4, 2022
PubMed
Summary
This summary is machine-generated.

Mifepristone effectively treats Cushing's syndrome by blocking the glucocorticoid receptor, improving symptoms like high blood sugar and blood pressure. Careful monitoring is essential due to potential side effects and hormonal changes.

Keywords:
ACTHAntiglucocorticoidCortisolCushingGlucocorticoidMifepristonePituitaryReceptor

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Area of Science:

  • Endocrinology
  • Pharmacology

Background:

  • Mifepristone is the sole approved glucocorticoid receptor antagonist for Cushing's syndrome.
  • Initially developed as an abortifacient, its efficacy in blocking glucocorticoid receptors was noted in case reports since 1985.

Purpose of the Study:

  • To review the efficacy and safety of mifepristone in managing Cushing's syndrome.
  • To discuss the clinical implications and management strategies for mifepristone treatment.

Main Methods:

  • Review of clinical data and case reports, including findings from the SEISMIC trial (2012).
  • Analysis of mifepristone's mechanism of action, clinical benefits, and adverse effects.

Main Results:

  • Mifepristone significantly improves clinical manifestations of Cushing's syndrome, including glycemia, blood pressure, muscle weakness, and body weight.
  • Treatment leads to increased cortisol and ACTH levels, necessitating management based on clinical signs rather than hormone levels.
  • Adverse effects include adrenal insufficiency, hypokalemia, and menorrhagia; drug-drug interactions due to CYP enzyme inhibition are also noted.

Conclusions:

  • Mifepristone is a valuable therapeutic option for severe Cushing's syndrome or cases resistant to other treatments.
  • Careful patient management and monitoring are crucial to mitigate potential adverse effects and drug interactions.
  • Development of alternative glucocorticoid receptor blockers without progesterone receptor activity is ongoing.