• The most common cause of Cushing's syndrome is iatrogenic from medically
prescribed corticosteroids.
• Excess cortisol production may be caused by either excess adrenocorticotropic
hormone (ACTH) secretion (from a pituitary or other ectopic tumor) or
independent adrenal overproduction of cortisol.
• The diagnosis can be challenging in mild cases.
• Endocrine Society (ES) recommends initial use of one test with high diagnostic accuracy
(urine free cortisol [UFC], late night salivary cortisol, 1-mg overnight or 2-mg 48-h
dexamethasone suppression test).
• Testing for Cushing's syndrome in certain high-risk populations has shown an
unexpectedly high incidence of unrecognized Cushing's syndrome as compared with the
general population. Although there are limited data on the prevalence of the syndrome
in these disorders, the diagnosis should be considered.
• Often patients have a number of features that are caused by cortisol excess but that
are also common in the general population such as obesity, depression, diabetes,
hypertension, or menstrual irregularity.
• As a result, there is an overlap in the clinical presentation of individuals with and
without the disorder. The distinction between these groups is difficult, and there is no
one correct diagnostic strateg y.
• There is a wide spectrum of clinical manifestations at any given level of
hypercortisolism. Because Cushing's syndrome tends to progress, accumulation
of new features increases the probability that the syndrome is present.
• Caregivers are encouraged to consider Cushing's syndrome as a secondary cause
of these conditions, particularly if additional features of the disorder are present.
If Cushing's syndrome is not considered, the diagnosis is all too often delayed.
• Cushing's syndrome tends to progress and severe hypercortisolism is probably
associated with a worse outcome, it is likely that early recognition and treatment
of mild disease would reduce the risk of residual morbidity.
Key Points
