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Endocrinology

Cushing Syndrome

Chronic glucocorticoid excess - most commonly iatrogenic; endogenous causes include pituitary ACTH-secreting adenoma (Cushing disease), ectopic ACTH (small-cell lung cancer, carcinoid) and adrenal adenoma/carcinoma.

Last reviewed 13 May 2026 - MedicoMedics editorial team

Adrenal cortical zones producing excess cortisol in Cushing syndrome

Pathophysiology

Excess cortisol suppresses ACTH (except in ACTH-dependent forms), drives gluconeogenesis, proteolysis, lipolysis with central redistribution, immunosuppression and mineralocorticoid receptor activation.

Sources: Endocrine Society CPG on Cushing Syndrome Treatment (J Clin Endocrinol Metab 2015;100:2807); Pituitary Society Consensus on Cushing Disease (Nat Rev Endocrinol 2021;17:337)

Clinical presentation

Central obesity, moon facies, buffalo hump, supraclavicular fat, purple abdominal striae (>1 cm), proximal myopathy, easy bruising, hypertension, glucose intolerance, hirsutism, osteoporosis, mood disturbance, poor wound healing.

Sources: Endocrine Society CPG on Cushing Syndrome Treatment (J Clin Endocrinol Metab 2015;100:2807); Pituitary Society Consensus on Cushing Disease (Nat Rev Endocrinol 2021;17:337)

Diagnosis

Screen: any two of - late-night salivary cortisol, 24-h urinary free cortisol, 1 mg overnight dexamethasone suppression test. Confirm hypercortisolism, then measure ACTH: suppressed -> adrenal imaging; normal/high -> high-dose dexamethasone and pituitary MRI +/- inferior petrosal sinus sampling.

Sources: Endocrine Society CPG on Cushing Syndrome Treatment (J Clin Endocrinol Metab 2015;100:2807); Pituitary Society Consensus on Cushing Disease (Nat Rev Endocrinol 2021;17:337)

Management

Iatrogenic: taper glucocorticoids. Pituitary adenoma: transsphenoidal resection (first-line, remission 70-90%). Adrenal tumour: adrenalectomy. Ectopic ACTH: resect source; medical therapy with ketoconazole, metyrapone, osilodrostat or mifepristone if surgery not feasible.

Sources: Endocrine Society CPG on Cushing Syndrome Treatment (J Clin Endocrinol Metab 2015;100:2807); Pituitary Society Consensus on Cushing Disease (Nat Rev Endocrinol 2021;17:337)

Complications

Cardiovascular disease (>4x mortality), diabetes, osteoporotic fractures, thromboembolism, opportunistic infections, and psychiatric morbidity even after biochemical cure.

Sources: Endocrine Society CPG on Cushing Syndrome Treatment (J Clin Endocrinol Metab 2015;100:2807); Pituitary Society Consensus on Cushing Disease (Nat Rev Endocrinol 2021;17:337)

Sample USMLE-style MCQs

Try 5 questions on this topic. Practice hundreds more free with a trial.

Question 1

Best initial screening test for Cushing syndrome?

Question 2

Suppressed ACTH with elevated cortisol suggests?

Question 3

Which is a Cushing-specific physical sign?

Question 4

A patient with small-cell lung cancer has hypokalaemia, hyperglycaemia, and high ACTH not suppressed by high-dose dexamethasone. Cause?

Related topics:lung cancer

Question 5

First-line therapy for pituitary Cushing disease?

References

Primary guidelines and peer-reviewed sources used for this entry. Reviewed 13 May 2026 by MedicoMedics editorial team.

Frequently asked

How do you distinguish pseudo-Cushing?

Alcohol use, depression, obesity and pregnancy can produce mild hypercortisolism. Late-night salivary cortisol, dex-CRH test, and clinical follow-up differentiate from true Cushing syndrome.

Why check both ACTH and cortisol?

ACTH-dependent (pituitary, ectopic) shows normal/high ACTH with high cortisol; ACTH-independent (adrenal, exogenous steroids) shows suppressed ACTH.

What is Nelson syndrome?

After bilateral adrenalectomy for Cushing disease, an untreated pituitary corticotroph tumour expands, causing hyperpigmentation and mass effects.

Which drug blocks glucocorticoid receptors?

Mifepristone - useful for hyperglycaemia in inoperable Cushing but does not lower cortisol.

Related conditions

High-yield topics students commonly study alongside Cushing Syndrome.

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