Ectopic adrenocorticotropin syndrome: diagnosis and treatment

Abstract

Purpose of reviewThis review will cover new insights into how the POMC gene is regulated in extra-pituitary tissues, and also will cover two major, long-term outcome studies of patients with ectopic adrenocorticotropin (ACTH) syndrome – one from London, UK, the other from the National Institutes of Health, USA. Recent findingsDifferential expression of the POMC gene in nonpituitary cells appears to require the POMC gene promoter to be in a demethylated state. This allows assembly of transcription factors on the DNA, and so expression of the gene. Targeting POMC methylation may therefore eventually offer a novel therapeutic option both for ectopic ACTH syndrome but also other POMC-related pathologies, including Cushing's disease, and obesity. In the last year two major series have been published, reviewing clinical experience of managing the ectopic ACTH syndrome on either side of the Atlantic. These reviews will be interpreted. SummaryEctopic ACTH syndrome remains rare in endocrine practice, but its true incidence is likely to be much higher in patients whose presentation is dominated by the causative malignancy. The syndrome provides insights into the basic mechanisms governing POMC gene expression in a cell-type specific manner, and in development. The majority of causative tumours are thoracic, and are imaged by combined plain radiology, computed tomography and magnetic resonance scanning.