Diagnostic Considerations

As noted earlier, owing to the generally nonspecific GI symptoms and signs of Zollinger-Ellison syndrome (ZES), particularly in children, the correct diagnosis may be delayed. When evaluating patients with suspected Zollinger-Ellison syndrome, also consider reflux disease, Barrett esophagitis, esophageal stenosis, and the following conditions:

Hypochlorhydria due to chronic atrophic gastritis
Prolonged proton pump inhibitor (PPI) use
GI bleeding
Gastric outlet obstruction

Differential Diagnoses

Workup

Massaro SA, Emre SH. Metastatic Gastrinoma in a Pediatric Patient With Zollinger-Ellison Syndrome. J Pediatr Hematol Oncol. 2013 Feb 15. [QxMD MEDLINE Link].
Gibril F, Schumann M, Pace A, Jensen RT. Multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: a prospective study of 107 cases and comparison with 1009 cases from the literature. Medicine (Baltimore). 2004 Jan. 83(1):43-83. [QxMD MEDLINE Link].
Imamura M, Komoto I, Ota S. Changing treatment strategy for gastrinoma in patients with Zollinger-Ellison syndrome. World J Surg. 2006 Jan. 30(1):1-11. [QxMD MEDLINE Link].
Zollinger RM, Ellison EH. Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg. 1955 Oct. 142(4):709-23; discussion, 724-8. [QxMD MEDLINE Link]. [Full Text].
Passaro E, Howard TJ, Sawicki MP, et al. The origin of sporadic gastrinomas within the gastrinoma triangle: a theory. Arch Surg. 1998 Jan. 133(1):13-6; discussion 17. [QxMD MEDLINE Link].
Debelenko LV, Emmert-Buck MR, Zhuang Z, et al. The multiple endocrine neoplasia type I gene locus is involved in the pathogenesis of type II gastric carcinoids. Gastroenterology. 1997 Sep. 113(3):773-81. [QxMD MEDLINE Link].
Kulke MH, Mayer RJ. Carcinoid tumors. N Engl J Med. 1999 Mar 18. 340(11):858-68. [QxMD MEDLINE Link].
Evans JT, Nickles S, Hoffman BJ. Primary hepatic gastrinoma: an unusual case of zollinger-ellison syndrome. Gastroenterol Hepatol (N Y). 2010 Jan. 6(1):53-6. [QxMD MEDLINE Link]. [Full Text].
Riff BP, Leiman DA, Bennett B, Fraker DL, Metz DC. Weight Gain in Zollinger-Ellison Syndrome After Acid Suppression. Pancreas. 2015 Jul 8. [QxMD MEDLINE Link].
Norton JA, Fraker DL, Alexander HR, et al. Surgery to cure the Zollinger-Ellison syndrome. N Engl J Med. 1999 Aug 26. 341(9):635-44. [QxMD MEDLINE Link].
Nord KS, Joshi V, Hanna M, et al. Zollinger-Ellison syndrome associated with a renal gastrinoma in a child. J Pediatr Gastroenterol Nutr. 1986 Nov-Dec. 5(6):980-6. [QxMD MEDLINE Link].
Morrow EH, Norton JA. Surgical management of Zollinger-Ellison syndrome; state of the art. Surg Clin North Am. 2009 Oct. 89(5):1091-103. [QxMD MEDLINE Link].
Eire PF, Rodriguez Pereira C, Barca Rodriguez P, Varela Cives R. Uncommon case of gastrinoma in a child. Eur J Pediatr Surg. 1996 Jun. 6(3):173-4. [QxMD MEDLINE Link].
Ito T, Jensen RT. Primary hepatic gastrinoma: an unusual case of zollinger-ellison syndrome. Gastroenterol Hepatol (N Y). 2010 Jan. 6(1):57-9. [QxMD MEDLINE Link]. [Full Text].
Heikenen JB, Pohl JF, Werlin SL. Octreotide in pediatric patients. J Pediatr Gastroenterol Nutr. 2002 Nov. 35(5):600-9. [QxMD MEDLINE Link].
Kim HU. Diagnostic and Treatment Approaches for Refractory Peptic Ulcers. Clin Endosc. 2015 Jul. 48 (4):285-90. [QxMD MEDLINE Link].
Berna MJ, Hoffmann KM, Serrano J, Gibril F, Jensen RT. Serum gastrin in Zollinger-Ellison syndrome: I. Prospective study of fasting serum gastrin in 309 patients from the National Institutes of Health and comparison with 2229 cases from the literature. Medicine (Baltimore). 2006 Nov. 85(6):295-330. [QxMD MEDLINE Link].
Berna MJ, Hoffmann KM, Long SH, Serrano J, Gibril F, Jensen RT. Serum gastrin in Zollinger-Ellison syndrome: II. Prospective study of gastrin provocative testing in 293 patients from the National Institutes of Health and comparison with 537 cases from the literature. evaluation of diagnostic criteria, proposal of new criteria, and correlations with clinical and tumoral features. Medicine (Baltimore). 2006 Nov. 85(6):331-64. [QxMD MEDLINE Link].
Proye C, Malvaux P, Pattou F, et al. Noninvasive imaging of insulinomas and gastrinomas with endoscopic ultrasonography and somatostatin receptor scintigraphy. Surgery. 1998 Dec. 124(6):1134-43; discussion 1143-4. [QxMD MEDLINE Link].
Norton JA, Melcher ML, Gibril F, Jensen RT. Gastric carcinoid tumors in multiple endocrine neoplasia-1 patients with Zollinger-Ellison syndrome can be symptomatic, demonstrate aggressive growth, and require surgical treatment. Surgery. 2004 Dec. 136(6):1267-74. [QxMD MEDLINE Link].
Epelboym I, Mazeh H. Zollinger-Ellison syndrome: classical considerations and current controversies. Oncologist. 2014 Jan. 19 (1):44-50. [QxMD MEDLINE Link].
Corleto VD, Annibale B, Gibril F, et al. Does the widespread use of proton pump inhibitors mask, complicate and/or delay the diagnosis of Zollinger-Ellison syndrome?. Aliment Pharmacol Ther. 2001 Oct. 15(10):1555-61. [QxMD MEDLINE Link].
Jensen RT. Gastrinomas: Advances in Diagnosis and Management. Neuroendocrinology. 2004. 80 Suppl 1:23-27. [QxMD MEDLINE Link].
Kwekkeboom DJ, de Herder WW, van Eijck CH, et al. Peptide receptor radionuclide therapy in patients with gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med. 2010 Mar. 40(2):78-88. [QxMD MEDLINE Link].
Citak EC, Taskinlar H, Arpaci RB, Apaydin FD, Gunay EC, Tanriverdi H, et al. Primary lymph node gastrinoma: a rare cause of abdominal pain in childhood. J Pediatr Hematol Oncol. 2013 Jul. 35(5):394-8. [QxMD MEDLINE Link].
Mozell EJ, Cramer AJ, O'Dorisio TM, Woltering EA. Long-term efficacy of octreotide in the treatment of Zollinger-Ellison syndrome. Arch Surg. 1992 Sep. 127(9):1019-24; discussion 1024-6. [QxMD MEDLINE Link].

Media Gallery

Somatostatin receptor scintigraphy in a young patient with Zollinger-Ellison syndrome. Besides physiologic uptake in the kidneys and the spleen, 2 pathologic hot spots are present, one in the area of the duodenum and another next to the pancreas.
Somatostatin receptor scintigraphy in a young patient with Zollinger-Ellison syndrome whose gastrinomas were resected. The LEFT (big) tumor was a periduodenal lymph node gastrinoma; the RIGHT tumor was a pancreatic gastrinoma. Despite negative findings on the scan, the patient remained hypergastrinemic, probably because of microscopic disease that escaped diagnostic imaging and surgical exploration.

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Author

Tiffany J Patton, MD Assistant Professor, Division of Pediatrics, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Comer Children's Hospital, University of Chicago Division of the Biological Sciences, The Pritzker School of Medicine

Tiffany J Patton, MD is a member of the following medical societies: American Academy of Pediatrics, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Nothing to disclose.

Chief Editor

Carmen Cuffari, MD Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Royal College of Physicians and Surgeons of Canada

Disclosure: Received honoraria from Prometheus Laboratories for speaking and teaching; Received honoraria from Abbott Nutritionals for speaking and teaching. for: Abbott Nutritional, Abbvie, speakers' bureau.

Acknowledgements

Jayant Deodhar, MD Associate Professor in Pediatrics, BJ Medical College, India; Honorary Consultant, Departments of Pediatrics and Neonatology, King Edward Memorial Hospital, India