(11.05) A Rare Case of Ectopic Adrenocorticotropic Hormone Syndrome Associated with a Pancreatic Neuroendocrine Tumor

Introduction : Ectopic adrenocorticotropic hormone syndrome (EAS) from pancreatic neuroendocrine tumors (PNET) is considered very rare with an incidence rate of 1-2 cases per million people per year. While more common functional PNET are known to produce gastrin, insulin, or glucagon, tumors that secrete adrenocorticotropic hormone (ACTH) and cause Cushing’s syndrome tend to be more aggressive and difficult to manage. In this case report, we present a rare case of Cushing’s syndrome due to EAS from PNET.

Case(s) Description : A 32-year-old female without significant past medical history presented to the hospital 2 months post-partum with progressively worsening abdominal pain and intermittent confusion. Her family reported darkening of her facial skin which had rapidly worsened over the last 2 weeks. Clinical exam revealed facial acne, coarse hair on the upper lip, pigmented facial skin and a maculopapular rash on her back. Other typical cushingoid features, such as central obesity, dorsal fat pad, and moon facies, were absent. Computed tomography of the abdomen and pelvis revealed a large, slightly hypoattenuating pancreatic body/tail mass measuring 9.1 x 8.4 x 7.9 cm without evidence of main pancreatic duct dilation. Additionally, there were multiple ill-defined, hypoattenuating, bilateral hepatic lesions with the largest mass measuring 9.8 x 7.8 x 7.7 cm. Labs revealed hyperglycemia and hypokalemia. She subsequently underwent endoscopic ultrasonography which showed a hypoechoic, irregular mass in the pancreatic body/tail. Final cytology of fine-needle aspiration biopsy of the pancreatic tail lesion yielded a well differentiated neuroendocrine tumor. Endocrine biochemical work up revealed a 24-hour urinary free cortisol of 2,024 mcg/24h (4-50 mcg/24h), a serum cortisol of 54.5 mcg/dL (5-23 mcg/dL) following an overnight dexamethasone suppression test, and an ACTH of 252 pg/mL (6-50 pg/mL). Oral ketoconazole was initiated to suppress her hypercortisolism in addition to octreotide to treat the PNET. She responded well to treatment and showed biochemical and clinical improvement with a recent AM cortisol of 14.4 mcg/dL (4-22 mcg/dL) and ACTH of 27 pg/mL. Given that she was deemed not to be a candidate for surgical resection of the tumor due to metastasis to both lobes of liver, she remains on medical treatment with ketoconazole and lanreotide. 

Discussion : Although rare, treating EAS caused by a PNET can be challenging due to its malignant behavior. However, our case demonstrates that successful medical management and improved quality of life is possible even at an advanced stage of disease. More research and data review need to be conducted to establish guidelines and recommendations in management of EAS from PNET.