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.
- Common findings such as central obesity, hypertension, diabetes, depression and menstrual change have low specificity alone; test when several progressive or unusual features cluster.
- First prove endogenous hypercortisolism with a validated test such as overnight dexamethasone suppression, repeated late-night salivary cortisol or repeated 24-hour urinary free cortisol selected by endocrinology.
- Shift work, alcohol excess, severe depression, acute illness, obesity, oestrogen, enzyme-inducing medicines, renal impairment and incorrect sample collection can distort screening results.
- After confirmation, ACTH localises the physiology: suppressed ACTH points toward adrenal autonomy, whereas detectable or raised ACTH requires pituitary-versus-ectopic investigation.
- Do not image the pituitary or adrenals before biochemical confirmation and ACTH classification. Incidental lesions are common and can create a convincing but false narrative.
- Treatment is cause-directed surgery where feasible. Medical cortisol blockade is specialist therapy used for rapid control, bridging, persistent disease or when surgery is unsuitable.
- Active Cushing syndrome increases infection, venous thromboembolism, cardiovascular, fracture and psychiatric risk; managing these comorbidities is part of endocrine treatment rather than an optional extra.
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.
Insomnia, depression, emotional lability, cognitive change or psychosis may coexist with opportunistic or muted infection. Severe behavioural change or sepsis requires urgent treatment while the endocrine diagnosis proceeds.
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.
- Repeat or confirm abnormal results rather than ordering immediate imaging; refer urgently when clinical severity is high even if the biochemical series is still being completed.