Professor of Pediatric and Alolescent Endocrinology
Primary Generalized Glucocorticoid Resistance and Hypersensitivitym p2021-06-28T11:01:46+00:00
Primary Generalized Glucocorticoid Resistance (PGGR) is a rare, familial or sporadic condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids, which leads to compensatory activation of the HPA axis and hypersecretion of ACTH in the systemic circulation. On the other hand, Primary Generalized Glucocorticoid Hypersensitivity (PGGH) represents the mirror image of PGGR, and is characterized by generalized, partial, target-tissue hypersensitivity to glucocorticoids, and compensatory hypoactivation of the HPA axis. The molecular basis of these conditions has been attributed to mutations in the glucocorticoid receptor (hGR) gene, which impair glucocorticoid signal transduction and alter tissue sensitivity to glucocorticoids. To date, 17 mutations of the hGR gene have been associated with PGGR and 1 with PGGH.
During her years at the NIH and later at the BRFAA, Professor Evangelia Charmandari studied the molecular mechanisms of glucocorticoid action and in particular the molecular mechanisms underlying the syndromes of Primary Generalized Glucocorticoid Resistance and Hypersensitivity. She identified five novel mutations of the hGR gene in patients with those conditions and determined the molecular mechanisms through which various natural hGR mutants impair glucocorticoid signal transduction.
20. Nicolaides NC, Lamprokostopoulou A, Polyzos A, Kino T, Katsantoni E, Triantafyllou P, Christophoridis A, Katzos G, Dracopoulou M, Sertedaki A, Chrousos GP, Charmandari E.Transient Generalized Glucocorticoid Hypersensitivity. European Journal of Clinical Investigation 2015; 45(12): 1306-15.