From: The Endocrine Society
3.0. DIAGNOSIS OF CUSHING’S SYNDROME
Who should be tested
3.1. We recommend obtaining a thorough drug history to
exclude excessive exogenous glucocorticoid exposure leading
to iatrogenic Cushing’s syndrome before conducting
biochemical testing (1 ).
3.2. We recommend testing for Cushing’s syndrome in the
following groups:
• Patients with unusual features for age (e.g. osteoporosis,
hypertension) (Table 1) (1 )
• Patients with multiple and progressive features,
particularly those who are more predictive of Cushing’s
syndrome (Table 1) (1 )
• Children with decreasing height percentile and increasing
weight (1 )
• Patients with adrenal incidentaloma compatible with
adenoma (1 ).
3.3. We recommend against widespread testing for Cushing’s
syndrome in any other patient group (1 ).
Initial testing
3.4. For the initial testing for Cushing’s syndrome, we
recommend one of the following tests based on its suitability
for a given patient (Fig. 1) (1 ):
3.4.1. Urine free cortisol (UFC; at least two measurements)
3.4.2. Late-night salivary cortisol (two measurements)
3.4.3. 1-mg overnight dexamethasone suppression test
(DST)
3.4.4. Longer low-dose DST (2 mg/d for 48 h)
3.5. We recommend against the use of the following to test for
Cushing’s syndrome (1 ):
• Random serum cortisol or plasma ACTH levels
• Urinary 17-ketosteroids
• Insulin tolerance test
• Loperamide test
• Tests designed to determine the cause of Cushing’s
syndrome (e.g. pituitary and adrenal imaging, 8 mg DST).
3.6. In individuals with normal test results in whom the
pretest probability is high (patients with clinical features
suggestive of Cushing’s syndrome and adrenal incidentaloma
or suspected cyclic hypercortisolism), we recommend further
evaluation by an endocrinologist to confirm or exclude the
diagnosis (1 ).
3.7. In other individuals with normal test results (in whom
Cushing’s syndrome is very unlikely), we suggest reevaluation
in 6 months if signs or symptoms progress (2 ).
3.8. In individuals with at least one abnormal test result (for
whom the results could be falsely positive or indicate
Cushing’s syndrome), we recommend further evaluation by an
endocrinologist to confirm or exclude the diagnosis
(1 ).
Subsequent evaluation
3.9. For the subsequent evaluation of abnormal initial test
results, we recommend performing another recommended test
(Fig. 1, 1 ).
3.9.1. We suggest the additional use of the dexamethasone-
CRH test or the midnight serum cortisol test in specific
situations (Fig. 1, 1 ).
3.9.2. We suggest against the use of the desmopressin
test, except in research studies, until additional data validate
its utility (2 ).
3.9.3. We recommend against any further testing for
Cushing’s syndrome in individuals with concordantly negative
results on two different tests (except in patients suspected of
having the very rare case of cyclical disease) (1 ).
3.9.4. We recommend tests to establish the cause of
Cushing’s syndrome in patients with concordantly positive
results from two different tests, provided there is no concern
regarding possible non-Cushing’s hypercortisolism (Table 2)
(1 ).
3.9.5. We suggest further evaluation and follow-up for
the few patients with concordantly negative results who are
suspected of having cyclical disease and also for patients with
discordant results, especially if the pretest probability of
Cushing’s syndrome is high (2 ).
4.0. SPECIAL POPULATIONS/CONSIDERATIONS
4.1. Pregnancy: We recommend the use of UFC and against
the use of dexamethasone testing in the initial evaluation of
pregnant women (1 ).
4.2. Epilepsy: We recommend against the use of
dexamethasone testing in patients receiving antiepileptic
drugs known to enhance dexamethasone clearance and
recommend instead measurements of nonsuppressed cortisol
in blood, saliva, or urine (1 ).
4.3. Renal failure: We suggest using the 1-mg overnight DST
rather than UFC for initial testing for Cushing’s syndrome in
patients with severe renal failure (2 ).
4.4. Cyclic Cushing’s syndrome: We suggest use of UFC or
midnight salivary cortisol tests rather than DSTs in patients
suspected of having cyclic Cushing’s syndrome (2 ).
4.5. Adrenal incidentaloma: We suggest use of the 1-mg DST
or late-night cortisol test, rather than UFC, in patients
suspected of having mild Cushing’s syndrome (2 ).
