Diagnosis of Cushing’s Syndrome Guideline Resources

Full Guideline: The Diagnosis of Cushing’s Syndrome
JCEM | May 2008

Lynnette K. Nieman (Chair), Beverly M. K. Biller, James W. Findling, John Newell-Price, Martin O. Savage, Paul M. Stewart, Victor M. Montori

The 2008 guideline on the diagnosis of Cushing’s Syndrome:

  • Provides recommendations for the diagnosis of Cushing’s Syndrome
  • Emphasizes early recognition of Cushing’s Syndrome to reduce the risk of residual morbidity


Essential Points

  • 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 strategy.
  • 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.

Summary of Recommendations

+ 3.0 Diagnosis of Cushing's syndrome

+ 4.0 Special populations/considerations