SUN-907 Dual Ectopic Gastrin and ACTH Secretion Leading to Combined Zollinger-Ellison Syndrome and Cushing’s Syndrome in a Patient with Metastatic Neuroendocrine Pancreatic Tumor
Authors: Kwak Leigh , Lake Julia Caroline Wingate , Bal Simrun , Crawford Andrew Robert , Chaidarun Sushela S 
Published: May 2020

Background:

Zollinger-Ellison Syndrome (ZES) is caused by ectopic secretion of gastrin from a gastrinoma. The annual incidence of gastrinomas is 0.5 to 2 per million population1. Although 17-30% of gastrinomas will stain positive for both gastrin and ACTH, the clinical manifestation of both ZES and Cushing’s syndrome is rare. In a study by Maton et al., 3 of 59 patients (5%) with sporadic ZES (not MEN1) had Cushing’s syndrome as well2.

Clinical Case:

A 63yo woman with DM2 presented with persistent diarrhea for 2 years, and was diagnosed with ZES with a gastrin level of 1359 pg/mL (&lt;100 pg/mL). A CT A/P showed a 3.8 cm pancreatic tail mass with multiple liver lesions. These lesions showed positive uptake on octreoscan, and a biopsy was positive a pancreatic neuroendocrine (NE) tumor. Her diarrhea was controlled with a PPI and no other intervention was made.

7 months later, she experienced severe worsening of her DM control despite aggressive medication titration. Due to new confusion and lethargy, she presented acutely to the ED. Labs showed metabolic alkalosis and profound hypokalemia with a CO2 38 mmol/L (22 - 31 mmol/L), venous pH 7.58 (7.32 - 7.42) and K 2.1 mmol/L (3.5 – 5.0 mmol/L). Her skin was diffusely hyperpigmented, and she had numerous cushingoid features on exam including supraclavicular fat pads, round face, thin skin and thin extremities. A subsequent cortisol level was found to be 125 mcg/dL (AM [6-10 am] 4.8 – 19.5 mcg/dL) with an ACTH of 1081 pg/mL (6-50 pg/mL).

She was not an optimal candidate for adrenalectomy given previous abdominal surgeries. After an octreotide drip (total 1475 mcg in 24 hrs) failed to reduce cortisol levels, metyrapone 250 mg q6h was started which led to an immediate and significant reduction in cortisol (209 to 38 mcg/dL), improved quality of life and significant reduction in her insulin and K supplementation requirement.

Conclusion:

We present a rare case of a dual gastrin and ACTH-secreting metastatic pancreatic NE cancer, in which overt ZES preceded the relatively abrupt onset of clinical Cushing’s syndrome. Similar to Babu et al., the initial presentation was dominated by worsening DM control3. Despite the octreoscan positivity, cortisol production was not appreciably blocked by octreotide but was well controlled by metyrapone.

As seen in other cases, we again highlight the pluripotency of NE tumors and the ability to change hormone production. We also present the unique circumstance this patient faced for treatment options as she was not an optimal candidate for surgery.

Reference:

1. Oberg K. Pancreatic endocrine tumors. Semin Oncol. 2010 Dec;37(6):594-618.

2. Maton PN, Gardner JD, Jensen RT. Cushing’s syndrome in patients with the Zollinger-Ellison syndrome. N Engl J Med. 1986 Jul 3;315(1):1-5.

3. Babu AR, Dwarakanathan AA. Cushing’s syndrome from ectopic production of corticotropin by a metastatic gastrinoma. Endocr Pract. 2003 May-Jun;9(3):229-32.