Cushing’s Syndrome



  • Clinical syndrome due to chronic exposure to excess glucocorticoid hormones irrespective of the underlying cause.
    • Common ~0.6% of the population
      • can be due to endogenous causes (very rare ~2/1000000)
        • Corticotropin dependent (80-85%)
          • most commonly pituitary tumour (80% (/70%))
          • ectopic ACTH e.g. lung cancer
        • Corticotropin independent (20%)
          • usually adrenal adenoma (60% (/15%)) or carcinoma
      • Exogenous (common, around 1% of the population use exogenous steroids- around 70% of which have some adverse effects and 10% have overt Cushing’s syndrome)
      • Other causes include alcohol excess; major depression (biochem features only) and obesity (mild biochem profile and some clinical overlap)

Clinical Presentation


  • Features that best discriminate Cushing’s syndrome from other common conditions
    • Skin- Easy bruising (62%), facial plethora, purple striae
    • Musculoskeletal- Proximal muscle weakness (29%) and/or myopathy; early osteoporosis (50%) with or without vertebral fractures or osteonecrosis of femoral or humeral head
  • Other features
    • Headache (47%)
    • Skin and hair- thin skin, poor wound healing, hirsutism or scalp thinning; pigmentation (usually sign of ACTH dependent Cushings)
    • Weight gain/central obesity (97%); dorsocervical fat pad (buffalo hump); supraclavicular fat pads; facial fullness (moon face)
    • Reproductive system- menstrual irregularity; infertility
    • Psychiatric effects- depression (62%), psychosis, irritability, insomnia, fatigue
    • Diabetes (50%)
    • Cardiovascular- congestive cardiac failure; hypertension (74%); thrombosis
    • Immunosuppression
    • Visual disturbance may be a feature of primary Cushing’s disease (pituitary adenoma)
  • Make sure to ask about medications (exogenous steroid use)

Investigations (Endogenous Cushing’s)

  • Confirming Cushing’s syndrome
    • 1mg overnight dexamethasone suppression test
      • if cortisol >50nmol/l – suggests Cushing’s
      • NB Low dose dexamethasone suppression testing can also be used
        • However, requires regular administration of 0.5mg of steroid every 6 hours for 48 hours
    • 24 hour urinary free cortisol (elevated)
  • Identifying the cause
    • Plasma ACTH
      • >3.3pmol/l
        • ACTH-dependent
          • Pituitary MRI +/- bilateral inferior petrosal sinus sampling (BIPSS) with ACTH measurements
            • If negative, CXR +/- CT chest
      • <1.1pmol/l
        • ACTH independent
          • Adrenal CT
  • High-dose Dexamethasone suppression test
    • Can be used to help identify Cushing’s disease from other causes
    • 2mg dexamethasone every 6 hours for 48 hours.  If suppression of cortisol occurs, this suggests Cushing’s disease
  • Other tests include CRH test (a rise in cortisol and ACTH suggests pituitary cause)


  • Down-titrate any exogenous steroids where possible
  • Treat any underlying causes where possible
    • e.g. Trans-sphenoidal surgery +/- radiotherapy for pituitary tumours is routine

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: