Primary Generalized Glucocorticoid Resistance or Chrousos Syndrome: Allostasis Through a Mutated Glucocorticoid Receptor
December 2016
in “
Springer eBooks
”
Primary Generalized Glucocorticoid Resistance Chrousos Syndrome NR3C1 gene glucocorticoid receptor hypertension hypokalemic alkalosis hirsutism menstrual irregularities glucocorticoids transactivation ligand affinity coactivators GRIP1 dexamethasone suppression tests synthetic glucocorticoids glucocorticoid resistance glucocorticoid insensitivity high blood pressure low potassium alkalosis excessive hair growth period irregularities steroid hormones dexamethasone tests synthetic steroids
TLDR Chrousos Syndrome is caused by mutations that make the body less sensitive to glucocorticoids, leading to various symptoms and requiring high-dose treatment.
The document from December 3, 2016, examined Primary Generalized Glucocorticoid Resistance, also known as Chrousos Syndrome, which is caused by mutations in the NR3C1 gene that encodes the human glucocorticoid receptor (hGR). The syndrome leads to symptoms such as hypertension, hypokalemic alkalosis, hirsutism, and menstrual irregularities due to the body's partial insensitivity to glucocorticoids. The researchers studied the molecular mechanisms of mutant hGRs, finding that mutations can lead to decreased transactivation, reduced ligand affinity, and abnormal interactions with coactivators like GRIP1. A novel mutation was identified that caused a histidine to arginine substitution at amino acid position 726, resulting in various functional impairments of the receptor. Diagnostic approaches include personal and family history, endocrinologic evaluation, and dexamethasone suppression tests, while treatment typically involves high doses of synthetic glucocorticoids. The study highlighted the importance of recognizing the syndrome for proper management due to its varied clinical presentations.
