Synopsis
Recognise pathological cortisol excess, distinguish exogenous exposure from endogenous Cushing syndrome, localise ACTH dependence and manage its urgent cardiovascular, metabolic, infectious and thrombotic risks.
- Cushing syndrome means clinically important glucocorticoid excess from any cause; Cushing disease is specifically an ACTH-secreting pituitary corticotroph tumour.
- Exogenous glucocorticoid exposure is the commonest overall cause. Ask about tablets, injections, inhalers, creams, nasal sprays and unregulated products before ordering an endogenous-cortisol work-up.
- Discriminating features include facial plethora, easy bruising, wide violaceous striae, proximal myopathy, unexplained osteoporosis, thin skin, spontaneous hypokalaemia and growth failure with weight gain in a child.
Key red flags
Hyperpigmentation and androgen excess can accompany high ACTH, especially ectopic secretion or aggressive pituitary disease. Adrenal androgen excess with a large irregular mass raises concern for adrenocortical carcinoma.
Investigation priorities
Exclude exogenous exposure and identify drugs that invalidate biochemical tests.
Management branches
Multiple progressive discriminating features, unusual osteoporosis or hypertension, adrenal incidentaloma, or childhood growth failure with weight gain.
- Take a comprehensive steroid and medicine history, document objective features and identify acute infection, thrombosis, glucose or blood-pressure complications needing parallel treatment.
- Choose an appropriate first-line screen with endocrinology or the Society for Endocrinology pre-referral pathway, accounting for shift work, oestrogen, renal function and interacting medicines.
Key medicines
MetyraponeSpecialist-initiated divided regimen titrated to validated cortisol measurements or used in a block-and-replace strategy; follow current BNF and endocrine protocol.
Ketoconazole for endogenous Cushing syndromeEndocrine specialist dose increased according to cortisol response, liver tests, interactions and the licensed product information.