Clinical aspects of glucocorticoid sensitivity

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Published on: April 25, 2016

S W Lamberts1, A T Huizenga, P de Lange

  • 1Department of Medicine, Erasmus University, Rotterdam, The Netherlands.

Steroids
|April 1, 1996
PubMed

Insights

Genetic variations cause differing sensitivity to glucocorticoids in the population. Understanding this hypersensitivity and resistance is key to predicting safe and effective glucocorticoid dosages for patients.

Area of Science:

  • Pharmacogenomics
  • Endocrinology
  • Immunology

Background:

  • Glucocorticoids are widely used for their anti-inflammatory and immunosuppressive effects.
  • Individual responses to glucocorticoid therapy vary significantly, impacting treatment efficacy and safety.
  • Primary (hereditary) genetic variations in the glucocorticoid receptor gene influence systemic sensitivity.

Purpose of the Study:

  • To investigate the prevalence of hereditary glucocorticoid receptor gene abnormalities in the general population.
  • To differentiate between primary (hereditary) and acquired glucocorticoid resistance.
  • To inform personalized glucocorticoid dosing strategies and alternative treatment options.

Main Methods:

  • Analysis of genetic variations in the glucocorticoid receptor gene.
  • Clinical observation of patient responses to varying glucocorticoid doses.
  • Assessment of local inflammatory markers and cytokine profiles in patients with treatment resistance.

Main Results:

  • Approximately 6.6% of the population exhibit hereditary hypersensitivity to glucocorticoids.
  • Around 2.3% of individuals show hereditary resistance to glucocorticoids.
  • Acquired, localized glucocorticoid resistance, driven by local cytokine production, is common in inflammatory diseases like rheumatoid arthritis and asthma.

Conclusions:

  • Hereditary glucocorticoid receptor gene variations contribute to differential drug sensitivity and adverse effect profiles.
  • Acquired, localized glucocorticoid resistance in inflammatory sites necessitates alternative immunosuppressive therapies.
  • Personalized glucocorticoid therapy, considering genetic predisposition and acquired resistance, can optimize treatment outcomes.

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