Cushing Syndrome
Cushing syndrome is the clinical state of cortisol excess — first confirmed biochemically, then split by ACTH into ACTH-dependent (pituitary or ectopic) versus ACTH-independent (adrenal) causes, with adrenal causes treated by adrenalectomy plus steroid cover.
The big picture
Cortisol excess produces central obesity, a plethoric moon face, proximal myopathy, thin skin and easy bruising, hypertension, glucose intolerance and osteoporosis. The cause is either ACTH-driven (a pituitary adenoma — Cushing's disease — or an ectopic ACTH source) or ACTH-independent (a cortisol-secreting adrenal adenoma or carcinoma). Exogenous steroids are the commonest cause of all.
Confirm cortisol excess first, then let ACTH split adrenal (independent) from pituitary/ectopic (dependent) causes — and always give perioperative steroid cover after adrenalectomy for a cortisol-secreting tumour.
Mechanism pathway
Tap any step to see why it happens.
Symptom sorter
The common presentation.
Diagnostic algorithm
Each step answers one question. Tap to expand.
Treatment ladder
Confirm and localise, then treat the specific cause; for adrenal causes resect with glucocorticoid replacement of the suppressed contralateral gland.
Procedure chooser
- Adrenalectomy for a cortisol-secreting adrenal tumour (open en-bloc if adrenocortical carcinoma)
- Transsphenoidal pituitary surgery for Cushing's disease (managed by the relevant specialty)
Complications
- Hypertension, diabetes, osteoporosis, infections, thromboembolism, myopathy
- Adrenal insufficiency/crisis if steroid cover omitted after adrenalectomy
- Surgical complications
- Perioperative and tapering glucocorticoid replacement
- Confirm and localise before operating
- Treat adrenal crisis with steroids and fluids; taper replacement as the axis recovers
Follow-up
- Resolution of hypercortisolism and cardiometabolic features
- Recovery of the suppressed hypothalamic-pituitary-adrenal axis
- Recurrence
- Glucocorticoid replacement until the axis recovers after curative adrenalectomy
- Normalised cortisol, improving features, eventual axis recovery
- Persistent/recurrent hypercortisolism; adrenal insufficiency if cover omitted
- Recurrence or for the specific cause
- Prolonged steroid dependence during axis recovery; cardiometabolic and bone sequelae
Red flags
The contralateral gland is suppressed — risk of adrenal crisis. Always replace glucocorticoid.
Suspect adrenocortical carcinoma — surgical referral, avoid biopsy.
Consider ectopic ACTH — localise the source.
Summary tables
Localising Cushing syndrome by ACTH
| ACTH | Category | Cause / next step |
|---|---|---|
| Suppressed | ACTH-independent | Adrenal tumour → adrenal CT → adrenalectomy |
| Non-suppressed | ACTH-dependent | Pituitary (MRI/IPSS) or ectopic ACTH source |
Memory hooks
Confirm cortisol first, image later.
ACTH splits it: low = adrenal, high/normal = pituitary/ectopic.
Use ≥2 screening tests (DST, late-night salivary, urinary free cortisol).
Adrenalectomy for a cortisol tumour needs steroid cover.
Board traps
Adrenal Cushing operated without steroid cover → postoperative adrenal crisis.
Adrenal CT ordered before ACTH measurement.
Ectopic ACTH mistaken for pituitary disease without petrosal sinus sampling.
Clinical cases
A patient with central obesity, striae and proximal weakness has elevated urinary free cortisol and failed overnight dexamethasone suppression. Plasma ACTH is suppressed and CT shows a 3 cm adrenal adenoma.
What is the diagnosis, treatment, and a key perioperative requirement?