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Cushing syndrome
First exclude external steroids, then prove cortisol excess with two different screening tests, and only then measure ACTH to localise: low ACTH = adrenal, high or normal ACTH = pituitary (Cushing disease) or ectopic production.
Why it matters in the exam
The question presents a patient with central obesity, wide purple abdominal striae, fragile skin and bruising, proximal muscle weakness, hypertension, diabetes and osteoporosis. The candidate must choose a proper screening test: late-night salivary cortisol, 24-hour urinary free cortisol, or the overnight 1 mg dexamethasone suppression test — a morning cortisol above 1.8 µg/dL means no suppression. Two abnormal tests are needed. Well-known distractors: measuring ACTH or doing an MRI before cortisol excess is proven (incidental pituitary findings are common), and "pseudo-Cushing" in alcohol use disorder, depression and obesity.
Once excess is proven, ACTH guides the next step: low — an adrenal tumour (adrenal CT); high or normal — Cushing disease (pituitary MRI; if no clear finding, inferior petrosal sinus sampling) or ectopic ACTH production (small-cell lung cancer, carcinoid), which sometimes presents rapidly and severely with hypokalaemia. Treatment is surgical — transsphenoidal pituitary surgery or adrenalectomy — after which temporary adrenal insufficiency is expected and needs steroid replacement. When surgery is not possible: ketoconazole, metyrapone or osilodrostat.
Key points
- First exclude external steroids.
- Two screening tests: dexamethasone 1 mg (cortisol above 1.8 µg/dL), late-night saliva, 24-hour urine.
- Low ACTH = adrenal; high or normal = pituitary or ectopic.
- Hypokalaemia and a rapid course → ectopic ACTH production.
- Surgical treatment followed by temporary steroid replacement.
Summary table
| Step | Test | Interpretation | Exam note |
|---|---|---|---|
| Exclusion | Ask about steroids (including creams and inhalers) | The commonest cause | Before any test |
| Screening | Overnight dexamethasone 1 mg | Morning cortisol above 1.8 µg/dL = no suppression | Two abnormal tests are needed |
| Screening | Late-night salivary cortisol; 24-hour urinary free cortisol | High = cortisol excess | Pseudo-Cushing: alcohol, depression |
| Localisation | ACTH | Low = adrenal; high or normal = pituitary or ectopic | Only after excess is proven |
| ACTH-dependent | Pituitary MRI; petrosal sinus sampling | Cushing disease versus ectopic | Hypokalaemia points to ectopic |
| Treatment | Transsphenoidal surgery or adrenalectomy | Temporary steroid replacement afterwards | Drugs: ketoconazole, metyrapone, osilodrostat |
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Sources
- Endocrine Society Clinical Practice Guideline: The Diagnosis of Cushing's Syndrome, 2008 — Screening tests and their interpretation
- Consensus on diagnosis and management of Cushing's disease: a guideline update (Pituitary Society), 2021 — Localisation and treatment
- Harrison's Principles of Internal Medicine, 21st edition (2022) — Disorders of the Adrenal Cortex: Cushing's Syndrome
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-02. The text may contain errors; when in doubt, check the source.