Cushing's disease with 'normal suppression' due to decreased dexamethasone clearance

Suppression of urinary corticosteroids during low-dose dexamethasone testing (0.5 mg every six hours eight times) has commonly been recognized as a response that excludes the diagnosis of Cushing's syndrome. Although "normal suppression" has been reported previously in Cushing's disease, rarely has an explanation been provided for this aberrant response. We report a case of proven Cushing's disease in which normal suppression was observed with low-dose dexamethasone testing. Further study suggested that this phenomenon, which is not widely recognized, was related to an abnormally decreased clearance of dexamethasone. We therefore suggest that whenever responses to testing appear discordant with the clinical index of suspicion, simultaneous plasma dexamethasone and cortisol levels should be obtained to exclude abnormalities in dexamethasone clearance.