Cushing’s syndrome

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

Cushing’s facial appearance

Telangiectasia

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 
  • Bedtime salivary 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

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 (http://creativecommons.org/licenses/by/2.0). Sourced from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3436715/