Ectopic ACTH syndrome (EAS) is a rare cause of endogenous Cushing syndrome that can present with severe metabolic derangements and life-threatening cardiovascular complications.

An 82-year-old man with a 40-pack-year smoking history, dilated cardiomyopathy, heart failure with reduced ejection fraction, and hypertension presented with recurrent falls, peripheral oedema, and severe refractory hypokalaemia requiring urgent aeromedical transfer. Examination revealed florid cushingoid features, including central adiposity, ruddy facies, bruising, proximal myopathy, and oedema. Despite continuous intravenous potassium replacement, his serum potassium fell from 2.7 mmol/L to 1.9 mmol/L overnight, precipitating polymorphic ventricular tachycardia and subsequent cardiac arrest for which he was successfully resuscitated.

The combination of refractory hypokalaemia and cushingoid appearance prompted investigation for Cushing syndrome. Biochemical testing confirmed severe ACTH-dependent hypercortisolism. A high-dose dexamethasone suppression test demonstrated no cortisol suppression (1,686–1,900 nmol/L), supporting ectopic ACTH secretion. Given his smoking history, a pulmonary source was suspected. Bronchoscopy was deferred because of recent cardiac arrest and pulmonary oedema, with FDG-PET used for tumour localisation which confirmed a pulmonary source of the tumour.

Rapid cortisol control was achieved with metyrapone, ketoconazole, and subsequent hydrocortisone block-and-replace therapy. Following biochemical normalisation of urinary free cortisol and potassium, he commenced carboplatin-etoposide chemotherapy followed by maintenance immunotherapy. Venous thromboembolism and Pneumocystis jirovecii prophylaxis were also instituted. Three-month imaging demonstrated complete remission, permitting cessation of metyrapone.

EAS commonly presents with profound hypercortisolism and severe hypokalaemia. Early recognition, prompt biochemical confirmation, localisation of the ectopic source, and rapid initiation of steroidogenesis inhibitors are critical to reduce complications, including malignant arrhythmias, infection, thrombosis, and death.

This case highlights EAS as a rare but reversible cause of refractory hypokalaemia and cardiac arrest, emphasising the importance of recognising cushingoid features to enable timely diagnosis and lifesaving treatment.