Ectopic ACTH Syndrome from Metastatic Pancreatic Neuroendocrine Tumor

Presentation Number: MON 419
Date of Presentation: April 3rd, 2017

Paras B. Mehta*, Keta J. Pandit and Nalini Ram
Baylor College of Medicine, Houston, TX



Ectopic ACTH syndrome (EAS) comprises approximately 20% of cases of adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome. ACTH-secreting pancreatic neuroendocrine tumors (PNETs), although rare, are responsible for about 15% of EAS. We present a case of EAS arising from a metastatic PNET.

Clinical Case

A 40 year-old female with history of metastatic PNET and diabetes mellitus presented with several day history of altered mental status. On physical exam, she had skin hyperpigmentation, acne, moon facies and hirsutism. Initial laboratory investigation revealed hypokalemic metabolic alkalosis. Workup to confirm hypercortisolism revealed an elevated 24 hour urinary cortisol (1569 ug/24 hr, n < 50 ug/24 hr) and an elevated ACTH level (279 pg/dL, n 7.2 – 63.3 pg/dL), consistent with ACTH-dependent Cushing’s syndrome. A high-dose dexamethasone suppression test failed to suppress 8 a.m. cortisol (54.4 mcg/dL, n < 5 mcg/dL) and a CRH stimulation test did not yield an increase in cortisol of greater than 20% nor an increase in ACTH greater than 35%, both consistent with EAS. Pituitary MRI did not reveal any significant mass, further indicating an ectopic site as the source of ACTH.

The source for the patient’s ectopic ACTH was suspected to be her PNET. She had a history of biopsy-proven metastatic disease to the liver, lung, diaphragm, and ovaries, with increased uptake in the octreotide scan. ACTH staining of the resected ovarian tumors showed positive immunoreactivity, confirming the source of ACTH from the neuroendocrine tumor.

The patient was begun on ketoconazole therapy for medical management of her Cushing’s syndrome, and was noted to have improvement in hirsutism within 1 week. Oncology was consulted and plans to add a second chemotherapy agent to the patient’s current octreotide therapy in order to more aggressively treat the underlying PNET.


Pancreatic neuroendocrine tumors have been described as an exceedingly rare cause of EAS, with only 139 cases described in medical literature since 1946. This case demonstrates an algorithmic approach to the diagnosis of ectopic ACTH syndrome from a pancreatic neuroendocrine tumor. Additionally, this case demonstrates the importance of management of an underlying malignancy as well as the utility of steroidogenesis inhibitors in controlling hypercortisolism.


Nothing to Disclose: PBM, KJP, NR