PassFinals
Endocrinology & Metabolic

Cushing's Syndrome

Chronic glucocorticoid excess, usually caused by prescribed steroids, produces a recognisable catabolic and metabolic phenotype; endogenous disease needs specialist biochemical confirmation and source localisation.

In a nutshell

Cushing's syndrome is chronic glucocorticoid excess, usually exogenous. Look for progressive central obesity, proximal weakness, thin bruising skin and violaceous striae; exclude prescribed steroids, confirm endogenous hypercortisolism, then localise with ACTH and specialist imaging.

Classic presentation

Progressive central weight gain, rounded face, wide purple striae, proximal weakness, hypertension or diabetes, with a careful history of prescribed steroid exposure.

Key points

  • Cushing's syndrome means cortisol excess from any cause; Cushing's disease specifically means a pituitary ACTH-secreting adenoma.
  • Check oral, inhaled, topical, injected and repeated-course glucocorticoids before testing for endogenous disease.
  • Confirm hypercortisolism with a validated specialist test such as overnight dexamethasone suppression, late-night salivary cortisol or 24-hour urinary free cortisol.
  • After confirmation, suppressed ACTH suggests an adrenal source; detectable or raised ACTH suggests pituitary or ectopic ACTH.
  • Do not use high-dose dexamethasone suppression as a stand-alone localisation test; specialist teams may need pituitary MRI, targeted imaging or inferior petrosal sinus sampling.
  • Definitive treatment is source-directed surgery when feasible; cortisol-lowering drugs are specialist bridges or alternatives and require current BNF/local-protocol monitoring.
  • After treatment, monitor for adrenal insufficiency as well as recurrent cortisol excess and its cardiovascular, metabolic, bone, infectious and psychiatric complications.

First-line investigation

Exclude exogenous glucocorticoids, then refer for specialist biochemical confirmation with an appropriate cortisol-excess test; do not start localisation imaging from clinical appearance alone.

Management

Exclude exogenous steroid excess

  • Review every glucocorticoid route and safely taper only with the prescriber/endocrine team; plan for adrenal suppression and sick-day cover.1,4

Confirm and localise endogenous disease

  • Use validated cortisol-excess testing followed by ACTH and specialist imaging; discordant or equivocal results need endocrine review before surgery.1,3

Use source-directed treatment

  • Refer to a pituitary/adrenal/neuroendocrine MDT for surgery when feasible; use specialist cortisol-lowering medication if treatment is delayed, unsafe or incomplete.1,5,6

Treat complications

  • Actively manage hypertension, diabetes, hypokalaemia, bone disease, infection, thrombosis and psychiatric morbidity around definitive treatment.1,2,5

Monitor for recurrence and adrenal insufficiency

  • After source control, monitor cortisol recovery, adrenal insufficiency, recurrent hypercortisolism, treatment toxicity and long-term cardiovascular, metabolic and bone outcomes.2,5,4

Exam traps

  • Cushing's disease is the pituitary subtype, not a synonym for Cushing's syndrome.
  • A normal random cortisol does not exclude Cushing's syndrome and is not a suitable screening test.
  • Do not stop long-term glucocorticoids abruptly: iatrogenic Cushingoid features can coexist with adrenal suppression.
  • A pituitary incidentaloma does not prove Cushing's disease; correlate ACTH, biochemical confirmation and specialist localisation testing.
  • After curative treatment, low cortisol may reflect treatment-related adrenal insufficiency and needs endocrine follow-up.

Illustrations

Cortisol excess mechanismDiagram tracing cortisol's normal catabolic, gluconeogenic and immunosuppressive actions to the clinical features seen when they occur in excess.PassFinals · original
Cushingoid body habitusClinical photograph illustrating central obesity, moon face, dorsocervical fat pad and purple abdominal striae.Ozlem Celik, Mutlu Niyazoglu, Hikmet Soylu and Pinar Kadioglu, Wikimedia Commons · CC-BY-2.5
Diagnostic pathway for Cushing's syndromeFlowchart showing exclusion of exogenous steroid excess, confirmation of endogenous cortisol excess, ACTH-based localisation and specialist source-directed treatment.PassFinals · original

Key sources

  1. NICE CKS: Cushing's syndrome (UK primary-care recognition, investigation and referral pathway; access may require NHS/OpenAthens authentication)
  2. NHS: Cushing's syndrome (Symptoms, causes, diagnosis, treatment and complications)
  3. Endocrine Society: The Diagnosis of Cushing's Syndrome (Validated screening tests, confirmation and ACTH-based localisation)Published 1 May 2008
  4. NICE NG243: Adrenal insufficiency — recommendations (Safe glucocorticoid withdrawal, adrenal-insufficiency recognition and emergency prevention)Published 28 Aug 2024 | Updated 18 Dec 2024
  5. Endocrine Society: Treatment of Cushing's Syndrome (Source-directed surgery, medical control and post-treatment monitoring)Published 29 Jul 2015
  6. BNF: Metyrapone (Current specialist prescribing, interactions and monitoring; access may require NHS/OpenAthens authentication)
  7. BNF: Ketoconazole (Current specialist prescribing, interactions and hepatic-safety information; access may require NHS/OpenAthens authentication)

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.