Table of Contents
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
- Nelson’s syndrome = symptoms resulting from rapid enlargement of a pre-existing pituitary tumour after bilateral adrenalectomy
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)
- ↘ if cortisol is not suppressed, CT thorax (look for ectopic ACTH source)
- ↘ 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)
NB: Nelson’s syndrome is a complication if Cushing’s disease was the cause.
Complications
- Impaired glucose tolerance and diabetes mellitus
- Hypertension
- Osteoporosis