Medical Care

The goals of treatment in patients with Zollinger-Ellison syndrome (ZES) are medical control of gastric acid hypersecretion and surgical resection of the tumor. Inpatient care is aimed at first controlling the gastric acid hypersecretion. Once gastric acid hypersecretion is controlled, imaging studies should be obtained to localize the tumor and determine tumor extent.

If the patient is acutely ill, immediate control of gastric acid hypersecretion can be achieved with intravenous proton pump inhibitors. Previously, this was accomplished with histamine 2 (H2) receptor blockers. Intravenous pantoprazole was approved recently by the US Food and Drug Administration. Proton pump inhibitors are superior to H2 blockers for the control of gastric acid hypersecretion.

Patients who are candidates for surgical resection should be referred for resection of the tumor.

For patients with metastatic disease, chemotherapy, interferon, and octreotide may be helpful. The response to these agents in most studies has been low. Liver transplantation for hepatic metastasis also has been reported. For patients with a single confined liver metastatic lesion, surgical resection may be attempted.

Consultations

Consider consultation with a gastroenterologist, surgeon, oncologist, and/or an endocrinologist.

Surgical Care

All patients with sporadic Zollinger-Ellison syndrome (ZES) without hepatic metastases or medical contraindications to surgery are advised to undergo surgical resection of the tumor because this decreases the risk of developing liver metastases, which can decrease the survival of these patients.

The role and timing of surgical resection in patients with multiple endocrine neoplasia-type 1 (MEN 1) is less clear. An attempt at surgical resection has been recommended if the tumor is larger than 2.5 cm. Cure is rarely achieved by surgical resection in patients with MEN 1; however, it may reduce the risk of subsequent metastatic disease.

In a single-institution retrospective study with a median follow-up of 18 years from the time of the diagnosis of ZES, Mortellaro et al examined the long-term outcomes in 12 patients with MEN 1 and ZES from 1970 to the present.^[4]The pancreas (n = 10), duodenum (n = 4), lymph nodes (n = 3), and liver (n = 1) were the most commonly identified gastrinoma sites. A total of 15 celiotomies were performed, and surgeries included 4 each of distal pancreatectomies and acid-reducing procedures, 3 each of enucleation of pancreatic gastrinoma and duodenal resection, 1 pancreaticoduodenectomy, and 7 noted as other.^[4]There was 1 each of a patient with transient (3 y) biochemical postsurgical cure and liver metastasis of gastrinoma (but no deaths from metastatic gastrinoma).^[4]

Deaths included causes such as respiratory arrest (n = 1), possibly due to aspiration or pulmonary embolus, and nondisease related (n = 3). At the last follow-up, 7 patients were alive. The investigators observed patients with MEN 1 and ZES rarely achieve biochemical cures with surgery; however, extended surgical resection was not only not needed in resection of localized gastrinomas, but it was also associated with excellent long-term outcomes.^[4]

There is a case report of a young adolescent male with primary lymph node gastrinoma and liver metastasis that caused ZES. This patient was successfully managed with preoperative cytoreduction followed by surgical resection of the residual mass, which had a 100% response and 4-year followup.^[5]

Because gastrinoma is a rare tumor, surgical resection should be attempted only at centers with personnel experienced in treating affected patients.

Outpatient postoperative care

After surgical resection of a gastrinoma, patients should be assessed for evidence of recurrence with serum fasting gastrin levels, a secretin test, and SRS. The first evaluation should be performed at 3-6 months postresection and then, optimally, yearly thereafter.

Proton pump inhibitors can be continued with the goal of maintaining the basal acid output (BAO) below 10 mEq/h before the next dose of the proton pump inhibitors.

Medication

Mendelson AH, Donowitz M. Catching the zebra: clinical pearls and pitfalls for the successful diagnosis of Zollinger-Ellison Syndrome. Dig Dis Sci. 2017 Sep. 62(9):2258-65. [QxMD MEDLINE Link].
De Angelis C, Cortegoso Valdivia P, Venezia L, Bruno M, Pellicano R. Diagnosis and management of Zollinger-Ellison syndrome in 2018. Minerva Endocrinol. 2018 Jun. 43(2):212-20. [QxMD MEDLINE Link].
Krampitz GW, Norton JA. Current management of the Zollinger-Ellison syndrome. Adv Surg. 2013. 47:59-79. [QxMD MEDLINE Link].
Mortellaro VE, Hochwald SN, McGuigan JE, et al. Long-term results of a selective surgical approach to management of Zollinger-Ellison syndrome in patients with MEN-1. Am Surg. 2009 Aug. 75(8):730-3. [QxMD MEDLINE Link].
Singh D, Lal SB, Sood A, et al. Management of primary lymph nodal gastrinoma with liver metastases resulting in Zollinger-Ellison Syndrome. Clin Nucl Med. 2019 Jan. 44(1):e36-9. [QxMD MEDLINE Link].
Alexakis N, Neoptolemos JP. Pancreatic neuroendocrine tumours. Best Pract Res Clin Gastroenterol. 2008. 22(1):183-205. [QxMD MEDLINE Link].
Anderson MA, Carpenter S, Thompson NW. Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas. Am J Gastroenterol. 2000 Sep. 95(9):2271-7. [QxMD MEDLINE Link].
Azimuddin K, Chamberlain RS. The surgical management of pancreatic neuroendocrine tumors. Surg Clin North Am. 2001 Jun. 81(3):511-25. [QxMD MEDLINE Link].
Baffy G, Boyle JM. Association of Zollinger-Ellison syndrome with pancreatitis: report of five cases. Dig Dis Sci. 2000 Aug. 45(8):1531-4. [QxMD MEDLINE Link].
Berger AC, Gibril F, Venzon DJ. Prognostic value of initial fasting serum gastrin levels in patients with Zollinger-Ellison syndrome. J Clin Oncol. 2001 Jun 15. 19(12):3051-7. [QxMD MEDLINE Link].
Bloomfeld R, Bornstein J, Jowell P. A report of a gastrinoma localized preoperatively by endoscopic ultrasound only and a review of the approach to imaging in Zollinger- Ellison syndrome. Dig Dis. 1999. 17(5-6):316-8. [QxMD MEDLINE Link].
Brentjens R, Saltz L. Islet cell tumors of the pancreas: the medical oncologist's perspective. Surg Clin North Am. 2001 Jun. 81(3):527-42. [QxMD MEDLINE Link].
Cadiot G, Jais P, Mignon M. Diagnosis of Zollinger-Ellison syndrome. From symptoms to biological evidence. Ital J Gastroenterol Hepatol. 1999 Oct. 31 Suppl 2:S147-52. [QxMD MEDLINE Link].
Campana D, Piscitelli L, Mazzotta E. Zollinger-Ellison syndrome. Diagnosis and therapy. Minerva Med. 2005 Jun. 96(3):187-206. [QxMD MEDLINE Link].
Chien RN, Chen TC, Chiu CT. Primary calcified gastrinoma of the liver. Dig Dis Sci. 2001 Feb. 46(2):370-5. [QxMD MEDLINE Link].
Cisco RM, Norton JA. Surgery for gastrinoma. Adv Surg. 2007. 41:165-76. [QxMD MEDLINE Link].
Corleto VD, Annibale B, Gibril F. 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].
Desir B, Poitras P. Oral pantoprazole for acid suppression in the treatment of patients with Zollinger-Ellison syndrome. Can J Gastroenterol. 2001 Dec. 15(12):795-8. [QxMD MEDLINE Link].
Doherty GM. Rare endocrine tumours of the GI tract. Best Pract Res Clin Gastroenterol. 2005 Oct. 19(5):807-17. [QxMD MEDLINE Link].
Ellison EC, Sparks J. Zollinger-Ellison syndrome in the era of effective acid suppression: are we unknowingly growing tumors?. Am J Surg. 2003 Sep. 186(3):245-8. [QxMD MEDLINE Link].
Fernandez JA, Robles R, Marin C. Role of liver transplantation in the management of metastatic neuroendocrine tumors. Transplant Proc. 2003 Aug. 35(5):1832-3. [QxMD MEDLINE Link].
Gibril F, Chen YJ, Schrump DS. Prospective study of thymic carcinoids in patients with multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 2003 Mar. 88(3):1066-81. [QxMD MEDLINE Link].
Gibril F, Jensen RT. Comparative analysis of diagnostic techniques for localization of gastrointestinal neuroendocrine tumors. Yale J Biol Med. 1997 Sep-Dec. 70(5-6):509-22. [QxMD MEDLINE Link].
Gibril F, Lindeman RJ, Abou-Saif A. Retained gastric antrum syndrome: a forgotten, treatable cause of refractory peptic ulcer disease. Dig Dis Sci. 2001 Mar. 46(3):610-7. [QxMD MEDLINE Link].
Gibril F, Reynolds JC, Lubensky IA. Ability of somatostatin receptor scintigraphy to identify patients with gastric carcinoids: a prospective study. J Nucl Med. 2000 Oct. 41(10):1646-56. [QxMD MEDLINE Link].
Gibril F, Venzon DJ, Ojeaburu JV. Prospective study of the natural history of gastrinoma in patients with MEN1: definition of an aggressive and a nonaggressive form. J Clin Endocrinol Metab. 2001 Nov. 86(11):5282-93. [QxMD MEDLINE Link].
Hung PD, Schubert ML, Mihas AA. Zollinger-Ellison Syndrome. Curr Treat Options Gastroenterol. 2003 Apr. 6(2):163-170. [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].
Ito T, Igarashi H, Uehara H, Jensen RT. Pharmacotherapy of Zollinger-Ellison syndrome. Expert Opin Pharmacother. 2013 Feb. 14(3):307-21. [QxMD MEDLINE Link]. [Full Text].
Jensen RT, Gibril F. Somatostatin receptor scintigraphy in gastrinomas. Ital J Gastroenterol Hepatol. 1999 Oct. 31 Suppl 2:S179-85. [QxMD MEDLINE Link].
Kohan E, Oh D, Wang H, et al. Duodenal bulb mucosa with hypertrophic gastric oxyntic heterotopia in patients with Zollinger Ellison syndrome. Diagn Ther Endosc. 2009. 2009:298381. [QxMD MEDLINE Link]. [Full Text].
Lew EA, Pisegna JR, Starr JA. Intravenous pantoprazole rapidly controls gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. Gastroenterology. 2000 Apr. 118(4):696-704. [QxMD MEDLINE Link].
McIntyre TP, Stahlfeld KR, Sell HW Jr. Gastrinoma. Am J Surg. 2002 Jun. 183(6):666-7. [QxMD MEDLINE Link].
Metz DC, Forsmark C, Lew EA. Replacement of oral proton pump inhibitors with intravenous pantoprazole to effectively control gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. Am J Gastroenterol. 2001 Dec. 96(12):3274-80. [QxMD MEDLINE Link].
Metz DC, Soffer E, Forsmark CE. Maintenance oral pantoprazole therapy is effective for patients with Zollinger-Ellison syndrome and idiopathic hypersecretion. Am J Gastroenterol. 2003 Feb. 98(2):301-7. [QxMD MEDLINE Link].
Metz DC, Starr JA. A retrospective study of the usefulness of acid secretory testing. Aliment Pharmacol Ther. 2000 Jan. 14(1):103-11. [QxMD MEDLINE Link].
Mignon M, Cadiot G. Natural history of gastrinoma: lessons from the past. Ital J Gastroenterol Hepatol. 1999 Oct. 31 Suppl 2:S98-103. [QxMD MEDLINE Link].
Mussig K, Wehrmann M, Horger M, et al. Lymph node gastrinoma in multiple endocrine neoplasia type 1 - a diagnostic challenge. Exp Clin Endocrinol Diabetes. 2008 Oct. 116(9):554-7. [QxMD MEDLINE Link].
Ng T, Maziak DE, Shamji FM. Esophageal perforation: a rare complication of Zollinger-Ellison syndrome. Ann Thorac Surg. 2001 Aug. 72(2):592-3. [QxMD MEDLINE Link].
Norton JA. Gastrinoma: advances in localization and treatment. Surg Oncol Clin N Am. 1998 Oct. 7(4):845-61. [QxMD MEDLINE Link].
Norton JA. Surgery and prognosis of duodenal gastrinoma as a duodenal neuroendocrine tumor. Best Pract Res Clin Gastroenterol. 2005 Oct. 19(5):699-704. [QxMD MEDLINE Link].
Norton JA. Surgical treatment and prognosis of gastrinoma. Best Pract Res Clin Gastroenterol. 2005 Oct. 19(5):799-805. [QxMD MEDLINE Link].
Norton JA, Alexander HR, Fraker DL. Comparison of surgical results in patients with advanced and limited disease with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome. Ann Surg. 2001 Oct. 234(4):495-505; discussion 505-6. [QxMD MEDLINE Link].
Norton JA, Alexander HR, Fraker DL. Possible primary lymph node gastrinoma: occurrence, natural history, and predictive factors: a prospective study. Ann Surg. 2003 May. 237(5):650-7; discussion 657-9. [QxMD MEDLINE Link].
Norton JA, Fraker DL, Alexander HR. Surgery to cure the Zollinger-Ellison syndrome. N Engl J Med. 1999 Aug 26. 341(9):635-44. [QxMD MEDLINE Link].
Norton JA, Jensen RT. Current surgical management of Zollinger-Ellison syndrome (ZES) in patients without multiple endocrine neoplasia-type 1 (MEN1). Surg Oncol. 2003 Aug. 12(2):145-51. [QxMD MEDLINE Link].
Norton JA, Kivlen M, Li M. Morbidity and mortality of aggressive resection in patients with advanced neuroendocrine tumors. Arch Surg. 2003 Aug. 138(8):859-66. [QxMD MEDLINE Link].
Odelowo OO, Nidiry JJ, Zulu SH. Primary lymph node gastrinoma: a case report. J Natl Med Assoc. 2003 Feb. 95(2):168-71. [QxMD MEDLINE Link].
Orloff SL, Debas HT. Advances in the management of patients with Zollinger-Ellison syndrome. Surg Clin North Am. 1995 Jun. 75(3):511-24. [QxMD MEDLINE Link].
Ramdani A, Mignon M, Samoyeau R. Effect of pantoprazole versus other proton pump inhibitors on 24-hour intragastric pH and basal acid output in Zollinger-Ellison syndrome. Gastroenterol Clin Biol. 2002 Apr. 26(4):355-9. [QxMD MEDLINE Link].
Roy PK, Venzon DJ, Feigenbaum KM. Gastric secretion in Zollinger-Ellison syndrome. Correlation with clinical expression, tumor extent and role in diagnosis--a prospective NIH study of 235 patients and a review of 984 cases in the literature. Medicine (Baltimore). 2001 May. 80(3):189-222. [QxMD MEDLINE Link]. [Full Text].
Roy PK, Venzon DJ, Shojamanesh H. Zollinger-Ellison syndrome. Clinical presentation in 261 patients. Medicine (Baltimore). 2000 Nov. 79(6):379-411. [QxMD MEDLINE Link].
Saijo F, Naito H, Funayama Y. Octreotide in control of multiple liver metastases from gastrinoma. J Gastroenterol. 2003. 38(9):905-8. [QxMD MEDLINE Link].
Strader DB, Doppman DL, Orbuch M. Functional localization of pancreatic endocrine tumors. Mignon M, Jensen RT, eds. Endocrine Tumors of the Pancreas: Recent Advances in Research and Management. Basel, Switzerland: S Karger AG; 1995. Vol 23: 282-97.
Tartaglia A, Bianchini S, Vezzadini P. Biochemical diagnosis of gastroenteropancreatic endocrine tumors. Minerva Med. 2003 Feb. 94(1):1-7. [QxMD MEDLINE Link].
Termanini B, Gibril F, Reynolds JC. Value of somatostatin receptor scintigraphy: a prospective study in gastrinoma of its effect on clinical management. Gastroenterology. 1997 Feb. 112(2):335-47. [QxMD MEDLINE Link].
Zimmer T, Scherubl H, Faiss S. Endoscopic ultrasonography of neuroendocrine tumours. Digestion. 2000. 62 Suppl 1:45-50. [QxMD MEDLINE Link].
Zogakis TG, Gibril F, Libutti SK. Management and outcome of patients with sporadic gastrinoma arising in the duodenum. Ann Surg. 2003 Jul. 238(1):42-8. [QxMD MEDLINE Link].
Grobmyer SR, Hochwald SN. Reoperative surgery for the Zollinger-Ellison syndrome. Adv Surg. 2010. 44:327-46. [QxMD MEDLINE Link].
Wilson SD, Doffek KM, Krzywda EA, Quebbeman EJ, Christians KK, Pappas SG. Zollinger-Ellison syndrome associated with a history of alcohol abuse: coincidence or consequence?. Surgery. 2011 Dec. 150(6):1129-35. [QxMD MEDLINE Link].
Kanakis G, Kaltsas G. Biochemical markers for gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Best Pract Res Clin Gastroenterol. 2012 Dec. 26(6):791-802. [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].
Phan J, Benhammou JN, Pisegna JR. Gastric hypersecretory states: investigation and management. Curr Treat Options Gastroenterol. 2015 Dec. 13(4):386-97. [QxMD MEDLINE Link].
Sato Y, Hashimoto S, Mizuno K, Takeuchi M, Terai S. Management of gastric and duodenal neuroendocrine tumors. World J Gastroenterol. 2016 Aug 14. 22(30):6817-28. [QxMD MEDLINE Link].

Media Gallery

of 0

Author

Praveen K Roy, MD, MSc Clinical Assistant Professor of Medicine, University of New Mexico School of Medicine

Praveen K Roy, MD, MSc is a member of the following medical societies: Alaska State Medical Association, American Gastroenterological Association

Disclosure: Nothing to disclose.

Coauthor(s)

Sarah D Komanapalli, MBBS Resident Physician in Internal Medicine, Marshfield Clinic

Sarah D Komanapalli, MBBS is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Homayoun Shojamanesh, MD Former Fellow, Digestive Diseases Branch, National Institutes of Health

Homayoun Shojamanesh, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Showkat Bashir, MD Assistant Professor, Department of Medicine, Division of Gastroenterology, George Washington University, Washington, DC

Showkat Bashir, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Chief Editor

Philip O Katz, MD, FACP, FACG Chairman, Division of Gastroenterology, Albert Einstein Medical Center; Clinical Professor of Medicine, Jefferson Medical College of Thomas Jefferson University

Philip O Katz, MD, FACP, FACG is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Medtronic<br/>Received income in an amount equal to or greater than $250 from: Torax medical: pfizer consumer, .

Additional Contributors

Anil Minocha, MD, FACP, FACG, AGAF, CPNSS Professor of Medicine, Director of Digestive Diseases, Medical Director of Nutrition Support, Medical Director of Gastrointestinal Endoscopy, Internal Medicine Department, University of Mississippi Medical Center; Clinical Professor, University of Mississippi School of Pharmacy

Anil Minocha, MD, FACP, FACG, AGAF, CPNSS is a member of the following medical societies: American Academy of Clinical Toxicology, American Society for Gastrointestinal Endoscopy, American Federation for Clinical Research, American Association for the Study of Liver Diseases, American College of Forensic Examiners Institute, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous coauthor, Jehad Barakat, MD, to the development and writing of this article.

Zollinger-Ellison Syndrome Treatment & Management

Medical Care

Surgical Care

References

Tables

Contributor Information and Disclosures

What would you like to print?