Abstract Introduction Paraneoplastic ectopic ACTH syndrome (EAS) represents a dangerous intersection between pulmonology, oncology, and endocrinology. It is a rare emergency in small cell lung cancer (SCLC), characterized by rapidly progressive severe hypercortisolism with profound muscle weakness, edema, hypokalemia, hypertension, hyperglycemia, and frequent weight loss rather than classic cushingoid features—moon facies, striae, and weight gain. Excess cortisol activates mineralocorticoid receptors, producing treatment-resistant hypertension. Early recognition and rapid cortisol blockade with steroidogenesis inhibitors are essential to restore hemodynamic stability and enable oncologic care. Case A 79-year-old woman with previously treated right-lung SCLC presented with complete right-lung collapse, an enlarging hilar mass, and malignant effusion. Bronchoscopy revealed tumor infiltration not amenable to intervention. During hospitalization, she developed severe hypertension (systolic 170-200 mmHg) refractory to six antihypertensives, with hypokalemia, proximal weakness, and weight loss—features suggestive of EAS. Serum cortisol exceeded 120 µg/dL, plasma ACTH was 640 pg/mL, and dexamethasone suppression failed, confirming EAS. As metyrapone was unavailable regionally, ketoconazole 200 mg three times daily was initiated. By day 5, blood pressure stabilized below 140 mmHg, hypokalemia corrected, and cortisol fell to 54 µg/dL, reflecting rapid biochemical and hemodynamic improvement. She remained on hydralazine, metoprolol, lisinopril, spironolactone, and amlodipine. Osilodrostat, the preferred long-term 11β-hydroxylase inhibitor, was delayed by insurance; low-dose ketoconazole was continued. Despite endocrine stabilization, the patient experienced progressive respiratory decline and was transitioned to comfort care, passing away on day 15 of hospitalization. Discussion EAS occurs in 5-10% of SCLC cases and portends poor outcomes, with significantly reduced survival (median 6.6 vs 13.1 months in those without paraneoplastic syndromes) and lower first-line chemotherapy response rates (47.6% vs 70%). They often present with multiple metastatic sites, poor performance status and limited response to tumor relapses, often leading to early palliative management. As hypertension is mineralocorticoid-driven rather than RAAS-mediated, rapid initiation of steroidogenesis inhibitors—metyrapone, ketoconazole, osilodrostat, or etomidate—is supported by retrospective studies, systematic reviews, and NCCN, CHEST, and Endocrine Society guidelines. Ketoconazole inhibits 11β- and 17α-hydroxylase, rapidly lowering cortisol synthesis. Osilodrostat, a selective 11β-hydroxylase inhibitor, FDA-approved for Cushing’s disease, is used off-label in EAS for sustained control. IV etomidate and adrenalectomy are reserved for refractory cases. Conclusion EAS should be promptly recognized in SCLC patients with resistant hypertension, hypokalemia, and muscle weakness. Early cortisol blockade with steroidogenesis inhibitors stabilizes hemodynamics and enables oncologic care. Transition to osilodrostat provides sustained control. Multidisciplinary pulmonology, oncology, and endocrinology coordination are vital to improving survival in this high-risk population. This abstract is funded by: nil
Modi et al. (Fri,) studied this question.