Endogenous subclinical hypercortisolism: Diagnostic uncertainties and clinical implications

Subclinical hypercortisolism (SH) is a newly characterized hormonal disorder that is almost exclusively detected in the context of incidentally discovered adrenal masses. The diagnostic criteria used for the definition of this condition are at present controversial. Amongst the various tests used for the detection of this abnormality (dexamethasone suppression, urinary free cortisol, ACTH levels, midnight serum or salivary cortisol concentrations, ACTH responses to CRH stimulation), the dexamethasone suppression tests (DST) seem to better accomplish the task of unmasking subtle abnormalities of cortisol secretion. Several versions of DST have been used: the 1-mg overnight, the 3-mg overnight and the classical 2-day low-dose DST. This latter test has the theoretical advantage that, by more efficiently suppressing pituitary ACTH secretion, it may provide a measure of the residual (ie non-ACTH-dependent) cortisol secretion from the adrenal mass. In this way, post-dexamethasone cortisol concentrations may quantify the degree of autonomous cortisol hypersecretion. In fact, post-dexamethasone cortisol concentrations have a negative correlation with basal ACTH levels and a positive correlation with midnight cortisol concentrations as well as the size of the incidentally discovered adrenal mass. Most of the existing data indicate that SH detected in the context of adrenal incidentalomas may have some clinically significant implications. In fact, patients with higher post-dexamethasone cortisol concentrations demonstrate higher lipid levels and lower bone mass densities. It has also been suggested that SH may be responsible for biochemical and phenotypic changes reminiscent of the metabolic syndrome. In summary, SH does exist and is associated with a negative impact in patients' health; however, hormonal cut-off criteria for decision-making remain to be defined.