diagnosis of Cushing's syndrome

Last edited 04/2021 and last reviewed 07/2021

Diagnosis of Cushing's syndrome

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Who should be tested

Testing for Cushing's syndrome is recommended in the following groups (1):

  • Patients with unusual features for age (e.g. osteoporosis, hypertension)

  • Patients with multiple and progressive features, particularly those who are more predictive of Cushing's syndrome
    • Features that best discriminate Cushing's syndrome; most do not have a high sensitivity
      easy bruising
      facial plethora
      proximal myopathy (or proximal muscle weakness)
      striae (especially if reddish purple and > 1 cm wide)
      on children, weight gain with decreasing growth velocity


    • Cushing's syndrome features in the general population that are common and/or less discriminatory
      depression dorsocervical fat pad ("buffalo hump")  
      fatigue facial fullness  
      weight gain obesity  
      back pain supraclavicular fullness  
      changes in appetite thin skin  
      decreased concentration peripheral edema  
      decreased libido acne  
      impaired memory (especially short term) hirsutism or female balding  
      insomnia poor skin healing
      irritability
      menstrual abnormalities
      in children, slow growth in children, abnormal genital virilization
      in children, short stature
      in children, pseudoprecocious puberty or delayed puberty


  • children with decreasing height percentile and increasing weight

  • patients with adrenal incidentaloma compatible with adenoma

The following tests are advised NOT to be used 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)

For the initial testing for Cushing's syndrome, one of the following tests based on its suitability for a given patient, is recommended (1):

  • urine free cortisol (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)

Diagnostic criteria that suggest Cushing's syndrome are UFC greater than the normal range for the assay, serum cortisol greater than 1.8 mug/dl (50 nmol/liter) after 1 mg dexamethasone (1-mg DST), and late-night salivary cortisol greater than 145 ng/dl (4 nmol/liter).

Subsequent evaluation based on expert advice

Reference:

  • Nieman LK et al. The Diagnosis of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline.J Clin Endocrinol Metab. 2008 May; 93(5): 1526-1540.