Ectopic ACTH- and/or CRH-Producing Pheochromocytomas

Context: The characteristics of catecholamine-secreting pheochromocytomas have been well studied. However, less is known about the characteristics, management and outcome in patients with ectopic adrenocorticotropic hormone (ACTH) and/or corticotrophin-releasing hormone (CRH)-secreting pheochromocytomas.

Objective: To review the characteristics and outcomes of ACTH- and/or CRH-secreting pheochromocytomas.

Data source: A systematic search of PubMed/MEDLINE and Web of Science, identifying relevant reports published up to 10 February 2020.

Study selection: Original articles, including case reports and case series, reporting individual patient data from patients with ACTH- and/or CRH-secreting pheochromocytomas.

Data extraction: Information on sex, age, symptoms at presentation, comorbidities, biochemistry, imaging, histopathology, and outcomes was extracted.

Data synthesis: We identified 91 articles reporting on 99 cases of ACTH- and/or CRH-secreting pheochromocytomas (CRH-secreting n = 4). Median age at diagnosis was 49 years (interquartile range 38-59.5) with a 2:1 female to male ratio. Most patients presented with clinical Cushing syndrome (n = 79; 81%), hypertension (n = 87; 93%), and/or diabetes (n = 50; 54%). Blood pressure, glucose control, and biochemical parameters improved in the vast majority of patients postoperatively. Infections were the most common complication. Most cases (n = 70, 88%) with reported long-term outcome survived to publication (median follow-up 6 months).

Conclusion: Ectopic ACTH- and/or CRH-secreting pheochromocytoma should be considered in patients presenting with ACTH-dependent Cushing syndrome and adrenal mass. Despite the challenge in diagnosis, patient outcomes appear favorable.