Table of Contents TerminologyCauses Clinical features Investigations Confirming Cushing’s syndromeLocalising causative lesionManagement Try some questionsTry a Cushing’s OSCE station Learn the focussed examination too…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 Terminology Cushing’s syndrome = symptoms/signs resulting from chronic glucocorticoid excessCushing’s disease = ACTH-producing pituitary tumour causing Cushing’s syndrome Causes ACTH-dependentCushing’s disease (i.e. ACTH-secreting pituitary tumour)Ectopic ACTH secretion (small cell lung cancer most common cause)ACTH-independentIatrogenic (steroid treatment) – most commonAdrenal adenoma/carcinomaAdrenal hyperplasia Clinical features Fat redistribution: weight increase, central obesity, cushingoid facial features (facial mooning), interscapular and supraclavicular fat padsSkin: bruising, skin thinning, purple abdominal striaeHyperpigmentation (ACTH-dependent causes)Mood changesProximal myopathy Cushing’s facial appearanceTelangiectasia 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 testMidnight 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 neededTreat causeResect 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? Oops! This section is restricted to members. What is Nelson’s syndrome? Oops! This section is restricted to members. How do metyrapone and ketoconazole work in Cushing’s syndrome? Oops! This section is restricted to members. Try a Cushing’s OSCE station Cushing’s disease focussed examFind more stations here