Ectopic ACTH-secreting pheochromocytoma presenting as acute psychosis, hypertensive crisis and vascular acute abdomen: a systematic review

Abstract

Introduction: Ectopic ACTH-secreting pheochromocytoma is an extremely rare cause of Cushing syndrome with heterogeneous clinical manifestations often lacking typical Cushingoid features (Huang et al., 2025; Rifai et al., 2024). These tumors can co-secrete catecholamines and ACTH, creating a "glucocorticoid-driven positive feedback vicious cycle" that rapidly progresses to multisystem crisis (Inoue et al., 2018; Nakahira et al., 2025). Objective: To synthesize evidence on ectopic ACTH-secreting pheochromocytoma, emphasizing atypical presentations, diagnostic strategies and perioperative management. Methodology: Systematic review following PRISMA 2020 (Page et al., 2021). Search in PubMed, LILACS, SciELO and Cochrane for studies published between 1980 and 2026. Case reports, case series and systematic reviews were included. Quality was assessed using the adapted Newcastle-Ottawa scale (Wells et al., 2000). Results: Six relevant studies were identified. Acute psychosis can be the initial manifestation, resolving with cortisol normalization (Huang et al., 2025). Hypertensive crisis is refractory and requires alpha-blockade combined with cortisol synthesis inhibitors (Inoue et al., 2018). Vascular acute abdomen is due to mesenteric ischemia from catecholamine-induced vasospasm and paralytic ileus (Karri et al., 2005; Mazaki et al., 2002). The "vicious cycle" is interrupted by metyrapone, which simultaneously reduces cortisol, ACTH and catecholamines (Inoue et al., 2018). Conclusion: Ectopic ACTH-secreting pheochromocytoma represents a rare but lethal "destructive paradigm." All patients with ACTH-dependent Cushing syndrome and an adrenal mass should be screened for metanephrines. Preoperative identification and blockade of the glucocorticoid-driven positive feedback loop is critical to avoid intraoperative catecholamine crisis.