Diagnosis
Who Should Be Tested
➤ ES recommends obtaining a thorough drug history to exclude excessive
exogenous glucocorticoid exposure leading to iatrogenic Cushing's syndrome
before conducting biochemical testing (1|⊕⊕⊕⊕).
➤ ES recommends 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|⊕
).
➤ ES recommends against widespread testing for Cushing's syndrome in any other
patient group (1|⊕
).
Initial Testing
➤ For the initial testing for Cushing's syndrome, ES recommends one of the
following tests based on its suitability for a given patient (Fig. 1) (1|⊕
):
• UFC (at least two measurements)
• Late-night salivary cortisol (two measurements)
• 1-mg overnight dexamethasone suppression test (DST)
• Longer low-dose DST (2 mg/d for 48 h)
➤ ES recommends 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).
➤ 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), ES recommends further
evaluation by an endocrinologist to confirm or exclude the diagnosis (1|⊕
).
➤ In other individuals with normal test results (in whom Cushing's syndrome
is very unlikely), ES suggests reevaluation in 6 months if signs or symptoms
progress (2|⊕
).
