Endogenous subclinical hypercortisolism: Diagnostic uncertainties and clinical implications

Abstract

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.

Effects of sex steroids on bone in women with subclinical or overt endogenous hypercortisolism

“…The diagnosis of overt hypercortisolism was made on the basis of the typical clinical signs and symptoms and inappropriately elevated values of serum F and urinary free F (UFF) excretion. The diagnosis of subclinical Cushing's syndrome was based on the lack of typical clinical features (striae rubrae, moon face, gibbous, visceral obesity, and peripheral muscular atrophy) in the presence of adrenal mass and at least two abnormalities in functional tests of the hypothalamic-pituitaryadrenal axis (HPA) (24)(25)(26). The incomplete inhibition of serum cortisol levels (O30 ng/ml) after an overnight 1 mg dexamethasone (DXM) suppression test was the abnormality that was always required, since it has a high specificity to detect autonomous adrenal function (27).…”

Bilateral and unilateral adrenal incidentalomas: biochemical and clinical characteristics

“…It is reported in the 5-30% of patients with AI, accordingly to the various diagnostic criteria used in the literature (8,9,10). In patients with BAI, the prevalence of SH has been reported to be even higher, in relation to the tumour size (11).…”

Pros and cons of dexamethasone suppression test for screening of subclinical Cushing’s syndrome in patients with adrenal incidentalomas

“…Various diagnostic algorithms (biochemical testing procedures) have been used (1-4, 9, 10, 19, 20, 21) but they are often too complex and expensive to be applied for the endocrine work up of frequent tumours like adrenal adenomas, which may be detected serendipitously in about 4% of the patients undergoing abdominal CT (8). The overnight DST is convenient and appropriate for screening but it is still debated which cut-points and dexamethasone doses are more sound (21).…”