Generalized Glucocorticoid Resistance
January 2008
in “
US endocrinology
”
TLDR Mutations in the glucocorticoid receptor gene cause reduced sensitivity to glucocorticoids and may lead to poor response to treatment.
The 2007 document discussed primary generalized glucocorticoid resistance, a rare condition caused by mutations in the human glucocorticoid receptor (hGR) gene. These mutations reduce tissue sensitivity to glucocorticoids, leading to increased activity of the hypothalamic–pituitary– adrenal (HPA) axis and higher levels of cortisol and adrenocorticotropic hormone (ACTH). The study found that all mutant receptors showed a variable reduction in their ability to respond to dexamethasone, slower translocation into the nucleus, and defective interaction with the GRIP1 co-activator. The document also noted that failure to respond to glucocorticoid therapy, or the need for chronic glucocorticoid treatment, is common among patients and may be due to the process of inflammation, the disease itself, or the patient's genetic background.
