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Ectopic ACTH syndrome due to small-cell lung cancer — SCE Respiratory MCQ

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HardEndocrinologyEctopic ACTH syndrome due to small-cell lung cancerSCE Respiratory

A 66-year-old man with newly diagnosed extensive-stage small-cell lung cancer and liver metastases is being assessed before systemic anticancer treatment. Over 3 weeks he has developed profound proximal weakness, ankle oedema, hypertension and new hyperglycaemia. He has no classical centripetal obesity or purple striae. Serum potassium remains 2.3 mmol/L despite replacement, bicarbonate is 38 mmol/L and glucose is 16.8 mmol/L. His 09:00 serum cortisol is 1850 nmol/L, plasma ACTH is 238 ng/L and 24-hour urinary free cortisol is 11 times the upper limit of normal. Cortisol is not suppressed by overnight dexamethasone. Tumour cells express ACTH on immunohistochemistry. Alanine aminotransferase is 186 IU/L, attributed to extensive hepatic metastases. He is haemodynamically stable, alert and able to take oral medication. There is no clinical evidence of infection, active bleeding or previous heparin-induced thrombocytopenia. Which initial management plan is most appropriate?

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Correct answer: E — Start urgent oral metyrapone with potassium replacement, spironolactone, low-molecular-weight heparin and co-trimoxazole, then commence systemic anticancer treatment after initial metabolic stabilisation

Explanation lettering: C = shown as B · E = shown as C · B = shown as E

This is severe ectopic ACTH syndrome: very high cortisol, urinary free cortisol more than tenfold above normal, ACTH-dependent biochemistry and small-cell lung cancer are accompanied by life-threatening hypokalaemic alkalosis, hyperglycaemia and catabolic myopathy. Classical Cushingoid morphology may be absent because the onset is rapid. Hyper­cortisolism and its complications should be controlled urgently rather than awaiting tumour response. As he is stable and can absorb oral medication, metyrapone is an appropriate rapidly acting cortisol-synthesis inhibitor. Potassium replacement and mineralocorticoid-receptor antagonism address cortisol-mediated mineralocorticoid effects. Cortisol and electrolytes require close monitoring, with glucocorticoid replacement if treatment produces adrenal insufficiency. Severe Cushing syndrome also confers substantial venous-thromboembolism and opportunistic-infection risk; in the absence of contraindications, thromboprophylaxis and Pneumocystis prophylaxis are appropriate while definitive oncological treatment is organised. A exposes him to chemotherapy before correcting a major endocrine emergency. C is initially attractive because ketoconazole lowers cortisol, but marked hepatic dysfunction makes it a poor choice. D would be appropriate for critical deterioration, oral intolerance or inability to obtain rapid control orally; intensive-care etomidate is disproportionate here. E may be required for refractory, immediately life-threatening hypercortisolism when medical and tumour-directed control are unsuccessful, but it is not the preferred first intervention in a stable patient.

Reference: Metyrapone Esteve 250 mg Soft Capsules — Summary of Product Characteristics (22 April 2026; text revised 7 April 2026) — https://www.medicines.org.uk/emc/product/101077/smpc Therapeutic Strategies for the Treatment of Severe Cushing's Syndrome (2016) — https://pubmed.ncbi.nlm.nih.gov/26833215/ Cardiovascular risk assessment, thromboembolism, and infection prevention in Cushing's syndrome: a practical approach (2021) — https://pubmed.ncbi.nlm.nih.gov/33539319/