Cushing’s syndrome

Chronic glucocorticoid excess. Previously covered only in passing (adrenal incidentaloma, Addison’s causes) — this dedicated page pulls it together.

Causes

• Exogenous (by far the commonest) — prescribed or over-the-counter glucocorticoids (oral, inhaled, topical, injected).
• Endogenous:
  • ACTH-dependent — pituitary corticotroph adenoma (Cushing’s disease, ~70% of endogenous cases) or ectopic ACTH (e.g. small-cell lung cancer, carcinoid).
  • ACTH-independent — an adrenal adenoma or carcinoma autonomously secreting cortisol.

Clinical features

Centripetal obesity, moon facies, dorsocervical/supraclavicular fat pads, wide (>1 cm) purple striae, easy bruising and thin skin, proximal myopathy, hypertension, glucose intolerance/diabetes, osteoporosis, mood change, and (with androgen excess) hirsutism and menstrual disturbance. Features that best discriminate from simple obesity are proximal myopathy, wide purple striae, easy bruising and thin skin.

Investigations

Confirm cortisol excess with at least two first-line tests:

• 1 mg overnight dexamethasone suppression test (failure to suppress morning cortisol),
• late-night salivary cortisol (loss of diurnal rhythm), and/or
• 24-hour urinary free cortisol.

Exclude exogenous steroids and pseudo-Cushing’s states (alcohol, depression, severe obesity) first. Then localise (specialist-led): plasma ACTH (suppressed → adrenal source; normal/high → ACTH-dependent), followed by pituitary MRI, high-dose dexamethasone testing, and inferior petrosal sinus sampling as indicated.

Management

Refer to endocrinology. Withdraw exogenous glucocorticoids where possible (gradual taper to avoid adrenal insufficiency). Endogenous disease is treated at the source — transsphenoidal pituitary surgery for Cushing’s disease, adrenalectomy for adrenal tumours, treatment of an ectopic source — with medical cortisol-lowering therapy (e.g. metyrapone, ketoconazole) as an adjunct or when surgery is not feasible.