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Cushing’s syndrome

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Cushing’s syndrome focussed examination covered here!

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

Hypothalamic–pituitary–adrenal axis


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


  • 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


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


  • 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

What are the possible complications of Cushing’s syndrome?

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What is Nelson’s syndrome?

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How do metyrapone and ketoconazole work in Cushing’s syndrome?

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Try a Cushing’s OSCE station

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

Picture references

Cushing’s facial appearance: 2012. Ozlem Celik, Mutlu Niyazoglu, Hikmet Soylu and Pinar Kadioglu. Iatrogenic Cushing’s syndrome with inhaled steroid plus antidepressant drugs. Multidiscip Respir Med. 2012; 7(1): 26. Licenced under Creative Commons Attribution 2.0 Generic license ( Sourced from:

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