Cushing’s syndrome is a clinical syndrome characterised by the symptoms and signs that occur due to chronic glucocorticoid excess.

Terminology

• Cushing’s syndrome = symptoms/signs resulting from chronic glucocorticoid excess
• Cushing’s disease = ACTH-producing pituitary tumour causing Cushing’s syndrome

Causes

• ACTH-dependent
  • Cushing’s disease (i.e. ACTH-secreting pituitary tumour)
  • Ectopic ACTH secretion (small cell lung cancer most common cause)
• ACTH-independent
  • Iatrogenic (steroid treatment) – most common
  • Adrenal adenoma/carcinoma
  • Adrenal hyperplasia

Clinical features

• Fat redistribution: weight increase, central obesity, cushingoid facial features (facial mooning), interscapular and supraclavicular fat pads
• Skin: bruising, skin thinning, purple abdominal striae
• Hyperpigmentation (ACTH-dependent causes)
• Mood changes
• Proximal myopathy

Investigations

Confirming Cushing’s syndrome

• First-line tests – use one of:
  • Overnight dexamethasone suppression test (normally cortisol is suppressed by exogenous steroids, but not in Cushing’s syndrome)
  • 24-hour urinary cortisol 
• Second-line tests (if needed)
  • 48-hour dexamethasone suppression test
  • Midnight cortisol

Localising causative lesion

• Plasma ACTH 
  • If ACTH is low: CT adrenals (look for adrenal tumour/hyperplasia)
  • If ACTH is high: high-dose dexamethasone suppression test (ACTH from a pituitary tumour is still suppressible at high exogenous steroid doses, whereas ectopic ACTH is not)
    1. ↘ if cortisol is not suppressed, CT thorax (look for ectopic ACTH source)
    2. ↘ if cortisol is suppressed, MRI pituitary – if tumour not seen, it may be too small to visualise and bilateral petrosal sinus sampling may be required to make diagnosis

Management

• Metyrapone/ketoconazole to control symptoms if needed
• Treat cause
  • Resect tumour (e.g. transsphenoidal adenomectomy in Cushing’s disease)
  • Bilateral adrenalectomy (if source cannot be localised/recurrent post-surgery/bilateral adrenal hyperplasia).

Try some questions

Try a Cushing’s OSCE station

1. Cushing’s disease focussed exam
2. Find more stations here