Nonfunctioning adenomas and those causing preclinical and overt Cushing's syndrome may represent a continuum with clinical manifestations depending mainly on tumor size and HSD11B2 expression levels.
In particular, the transcript level of hsd11b2, a gene involved in the cortisol catabolism, was affected in prenatally stressed larvae, even after many hours from the removal of cortisol excess.
Relative deficiency of 11beta-HSD2 activity can occur in Cushing's syndrome due to saturation of the enzyme and explains the mineralocorticoid excess state that characterizes ectopic ACTH syndrome.
11beta-HSD2 protects the mineralocorticoid receptor from cortisol excess; mutations in the HSD11B2 gene explain an inherited form of hypertension, the syndrome of 'apparent mineralocorticoid excess', in which 'Cushing's disease of the kidney' results in cortisol-mediated mineralocorticoid excess.