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).