The Elusive Neuroendocrine Tumor: Finding the Ectopic ACTH Source 16 Years After the Diagnosis of Cushing Syndrome

Ectopic adrenocorticotropin hormone (ACTH) syndrome (EAS) accounts for the minority of cases of Cushing syndrome. Up to 20% of these cases remain occult, despite multiple imaging attempts to localize the ACTH-producing tumor. Here we describe long-term follow-up of a 41-year-old woman, with ectopic Cushing syndrome initially classified as occult due to negative localization studies, who had bilateral adrenalectomy to manage hypercortisolism. After 16 years and many computed tomography (CT) scans, magnetic resonance imaging scans, Octreoscans, and 2 exploration surgeries for false positives on imaging, the source of ectopic ACTH production was localized in the pancreas utilizing molecular imaging with gallium-68 somatostatin receptor–targeted positron emission tomography (PET)/CT and fluorine-18 fluorodeoxyglucose PET/CT. She underwent a distal pancreatectomy, and pathology confirmed a 1.7-cm well-differentiated pancreatic neuroendocrine tumor with a moderately strong reactivity to ACTH stain. This case demonstrates the utility of multiple functional imaging modalities in resolving these “cold cases” of occult ectopic Cushing syndrome and the importance of a timely management of hypercortisolism with bilateral adrenalectomy.