Cushing’s Syndrome
Separating MR from GR mediated effects is also very challenging in Cushing’s syndrome (CS), that is characterized by chronic glucocorticoid overproduction by the adrenal glands. Apart from a plethora of well-known metabolic and cardiovascular complications, there are several neuropsychiatric sequelae of increased endogenous glucocorticoid secretion (Piasecka et al. , 2020), as already noted by Harvey Cushing himself (Cushing, 1994). Additionally, brain atrophy due to excessive cortisol secretion has been repeatedly described in CS. Again, considering the important role of MR in emotional and cognitive functions, some of these alterations may be in part mediated by MR. Mifepristone, a GR antagonist, is used clinically in Cushing’s. Because of its GR antagonism, it may shift the MR/GR balance towards MR function which may have beneficial effects on depressive symptoms, cognitive function, and metabolic/cardiovascular risk factors (Howland, 2013).