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{{CMG}} {{AE}} {{MJK}}
 
{{CMG}} {{AE}} {{MJK}}, {{ARK}}
{{Zollinger-Ellison syndrome}}
{{Zollinger-Ellison syndrome}}
==Overview==
==Overview==
Patients with Zollinger-Ellison syndrome may experience abdominal pain and [[diarrhea]]. The diagnosis is also suspected in patients without symptoms who have severe ulceration of the stomach and small bowel, especially if they fail to respond to treatment.
Patients with Zollinger-Ellison syndrome may experience [[abdominal pain]] and [[diarrhea]]. The diagnosis is also suspected in patients without symptoms who have severe [[ulceration]] of the [[stomach]] and [[small bowel]], especially if they fail to respond to treatment. [[Gastrinoma]]s may occur as single [[tumors]] or as multiple, small tumors. About one-half to two-thirds of single [[Gastrinoma|gastrinomas]] are [[malignant]] tumors that most commonly spread to the [[liver]] and [[lymph node]]s near the [[pancreas]] and [[small bowel]]. Nearly 25 percent of patients with [[Gastrinoma|gastrinomas]] have multiple tumors as part of a condition called [[multiple endocrine neoplasia]] type I (MEN I). MEN I patients have tumors in their [[pituitary gland]] and [[parathyroid gland]]s in addition to tumors of the [[pancreas]]. Development of Zollinger-Ellison syndrome is the result of increased levels of [[gastrin]] due to an existing [[gastrinoma]] in the [[duodenum]] or [[pancreas]]. Zollinger-Ellison syndrome must be differentiated from gastric antrum syndrome, antral G-cell hyperplasia, [[peptic ulcer]], [[gastroesophageal reflux disease]] (GERD), and hypergastrinemia. The incidence of [[gastrinoma]], which can cause Zollinger-Ellison syndrome, is approximately 0.5-2 persons per 100,000 individuals worldwide. Pharmacologic medical therapies for Zollinger-Ellison syndrome include [[proton pump inhibitor]]s, [[H2-receptor antagonist]]s, [[chemotherapy]], and [[hormonal therapy]]. Effective measures for the primary prevention of Zollinger-Ellison syndrome include [[genetic testing]], if family history presents.


Gastrinomas may occur as single tumors or as multiple, small tumors. About one-half to two-thirds of single gastrinomas are [[malignant]] tumors that most commonly spread to the [[liver]] and [[lymph node]]s near the pancreas and small bowel. Nearly 25 percent of patients with gastrinomas have multiple tumors as part of a condition called [[multiple endocrine neoplasia]] type I (MEN I). MEN I patients have tumors in their [[pituitary gland]] and [[parathyroid gland]]s in addition to tumors of the pancreas.
==Historical Perspective==
==Historical Perspective==
Zollinger-Ellison syndrome was first discovered by Zollinger RM and Ellison EH in 1955.<ref name="wikipedia">Zollinger-Ellison syndrome 2015.https://en.wikipedia.org/wiki/Zollinger%E2%80%93Ellison_syndrome</ref>
In 1955, Zollinger and Ellison published their seminal paper on [[Gastrinoma|gastrinomas]] wherein the Zollinger-Ellison syndrome was first discussed.
 
==Pathophysiology==
==Pathophysiology==
Development of Zollinger-Ellison syndrome is the result of increased levels of [[gastrin]] due to an existing [[gastrinoma]] in the [[duodenum]] or [[pancreas]].<ref name="wikipedia">wikipedia.2015.https://en.wikipedia.org/wiki/Zollinger%E2%80%93Ellison_syndrome</ref>
Development of Zollinger-Ellison syndrome is the result of increased levels of [[gastrin]] due to an existing [[gastrinoma]] in the [[duodenum]] or [[pancreas]].
 
==Causes==
==Causes==
The cause of Zollinger-Ellison syndrome has not been identified. However, 25 to 30 percent of gastrinomas, which can cause Zollinger-Ellison syndrome, are caused by  multiple endocrine neoplasia type 1 ([[MEN1]]).<ref name="NIDDK">National Institute of Diabetes and Digestive and Kidney Diseases.http://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/zollinger-ellison-syndrome/Pages/facts.aspx#causes</ref>
The cause of Zollinger-Ellison syndrome has not been identified. However, 25 to 30 percent of gastrinomas, which can cause Zollinger-Ellison syndrome, are caused by  multiple endocrine neoplasia type 1 ([[MEN1]]).
 
==Differentiating Zollinger-Ellison syndrome from other Diseases==
==Differentiating Zollinger-Ellison syndrome from other Diseases==
Zollinger-Ellison syndrome must be differentiated from gastric antrum syndrome<ref name="pmid14201408">{{cite journal| author=SCOBIE BA, MCGILL DB, PRIESTLEY JT, ROVELSTAD RA| title=EXCLUDED GASTRIC ANTRUM SIMULATING THE ZOLLINGER-ELLISON SYNDROME. | journal=Gastroenterology | year= 1964 | volume= 47 | issue=  | pages= 184-7 | pmid=14201408 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14201408  }} </ref>, antral G-cell hyperplasia, [[peptic ulcer]], [[gastroesophageal reflux disease]] (GERD), and hypergastrinemia.
Zollinger-Ellison syndrome must be differentiated from [[stomach|gastric antrum syndrome]], [[stomach|antral G-cell hyperplasia]], [[peptic ulcer]], [[gastroesophageal reflux disease]] ([[GERD]]), and [[gastrin|hypergastrinemia]].
 
==Epidemiology and Demographics==
==Epidemiology and Demographics==
The incidence of [[gastrinoma]], which can cause Zollinger-Ellison syndrome, is approximately 0.5-2/million population/year worldwide.<ref name="pmid22261919">{{cite journal| author=Jensen RT, Cadiot G, Brandi ML, de Herder WW, Kaltsas G, Komminoth P et al.| title=ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes. | journal=Neuroendocrinology | year= 2012 | volume= 95 | issue= 2 | pages= 98-119 | pmid=22261919 | doi=10.1159/000335591 | pmc=PMC3701449 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22261919  }} </ref>. About 25 to 30 percent of gastrinomas are caused by  multiple endocrine neoplasia type 1 ([[MEN1]]).<ref name="NIDDK">National Institute of Diabetes and Digestive and Kidney Diseases.http://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/zollinger-ellison-syndrome/Pages/facts.aspx#causes</ref>
The incidence of [[gastrinoma]], which can cause Zollinger-Ellison syndrome, is approximately 0.05-0.2 per 100,000 individuals worldwide. About 25 to 30 percent of gastrinomas are caused by  multiple endocrine neoplasia type 1 ([[MEN1]]). Zollinger-Ellison syndrome is a disease that tends to affect the middle-aged adult population. Males are more commonly affected with Zollinger-Ellison syndrome than females.
 
==Natural History, Complications and Prognosis==
==Natural History, Complications and Prognosis==
If left untreated, patients with Zollinger-Ellison syndrome may progress to develop [[abdominal pain]], [[diarrhea]], and [[heartburn]]<ref name="pmid11144036">{{cite journal| author=Roy PK, Venzon DJ, Shojamanesh H, Abou-Saif A, Peghini P, Doppman JL et al.| title=Zollinger-Ellison syndrome. Clinical presentation in 261 patients. | journal=Medicine (Baltimore) | year= 2000 | volume= 79 | issue= 6 | pages= 379-411 | pmid=11144036 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11144036  }} </ref>. Common complications of Zollinger-Ellison syndrome include [[upper gastrointestinal bleeding]], [[anemia]], and [[duodenal ulcer perforation]]. Prognosis is generally good, and the 5 and 10-year survival rate of patients with Zollinger-Ellison syndrome is approximately 94% and 75%, respectively.<ref name="pmid7903006">{{cite journal| author=Melvin WS, Johnson JA, Sparks J, Innes JT, Ellison EC| title=Long-term prognosis of Zollinger-Ellison syndrome in multiple endocrine neoplasia. | journal=Surgery | year= 1993 | volume= 114 | issue= 6 | pages= 1183-8 | pmid=7903006 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7903006  }} </ref>
If left untreated, patients with Zollinger-Ellison syndrome may progress to develop [[abdominal pain]], [[diarrhea]], and [[heartburn]]. Common complications of Zollinger-Ellison syndrome include [[upper gastrointestinal bleeding]], [[anemia]], and [[duodenal ulcer perforation]]. Prognosis is generally good, and the 5 and 10-year survival rate of patients with Zollinger-Ellison syndrome is approximately 94% and 75%, respectively.


==Diagnosis==
==Diagnosis==
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Symptoms of Zollinger-Ellison syndrome include [[diarrhea]], [[odynophagia]], [[nausea]], and [[hematemesis]] .
Symptoms of Zollinger-Ellison syndrome include [[diarrhea]], [[odynophagia]], [[nausea]], and [[hematemesis]] .
===Physical Examination===
===Physical Examination===
Common physical examination findings of Zollinger-Ellison syndrome include epigastric [[tenderness]]<ref name="pmid7387166">{{cite journal| author=Drake DP, Maciver AG, Atwell JD| title=Zollinger-Ellison syndrome in a child: medical treatment with cimetidine. | journal=Arch Dis Child | year= 1980 | volume= 55 | issue= 3 | pages= 226-8 | pmid=7387166 | doi= | pmc=PMC1626767 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7387166  }} </ref>, [[pallor]], and [[jaundice]].
Common physical examination findings of Zollinger-Ellison syndrome include epigastric [[tenderness]], [[pallor]], and [[jaundice]].
 
===Laboratory Findings===
===Laboratory Findings===
An elevated concentration of fasting serum [[gastrin]] level and [[secretin]] stimulation test may be helpful in the diagnosis of Zollinger-Ellison syndrome.
An elevated concentration of fasting serum [[gastrin]] level and [[secretin|secretin stimulation test]] may be helpful in the diagnosis of Zollinger-Ellison syndrome.
 
===Abdominal CT===
===Abdominal CT===
Abdominal [[CT]] scan may be helpful in the diagnosis of Zollinger-Ellison syndrome caused by [[gastrinoma]]. [[Gastrinoma]]s are frequently multiple and often extrapancreatic (90% located in the gastrinoma triangle). Thus, they can be difficult to locate. For this reason, multiphase contrast enhanced thin slice cross-sectional imaging is ideal.<ref>Radiographic Features of Gastrinoma.Dr Frank Gaillard et al. Radiopaedia.org 2015. http://radiopaedia.org/articles/gastrinoma</ref> Findings on Abdominal CT scan suggestive of [[gastrinoma]] include clearly defined, well-enhanced mass.
Abdominal [[CT]] scan may be helpful in the diagnosis of Zollinger-Ellison syndrome caused by [[gastrinoma]]. [[Gastrinoma]]s are frequently multiple and often extrapancreatic (90% located in the gastrinoma triangle). Thus, they can be difficult to locate. For this reason, multiphase contrast enhanced thin slice cross-sectional imaging is ideal. Findings on Abdominal CT scan suggestive of [[gastrinoma]] include clearly defined, well-enhanced mass.
 
===Abdominal MRI===
===Abdominal MRI===
Abdominal MRI may be helpful in the diagnosis of Zollinger-Ellison syndrome caused by [[gastrinoma]]. Findings on abdominal MRI suggestive of Zollinger-Ellison syndrome include solitary lesion or multiple lesions.
Abdominal MRI may be helpful in the diagnosis of Zollinger-Ellison syndrome caused by [[gastrinoma]]. Findings on abdominal MRI suggestive of Zollinger-Ellison syndrome include solitary lesion or multiple lesions.
===Abdominal Ultrasound===
===Abdominal Ultrasound===
Abdominal [[ultrasound]] may be helpful in the diagnosis of Zollinger-Ellison syndrome caused by [[gastrinoma]].<ref name="HarveyPasieka2012">{{cite journal|last1=Harvey|first1=Adrian|last2=Pasieka|first2=Janice L.|last3=Al-Bisher|first3=Hassan|last4=Dixon|first4=Elijah|title=Primary Hepatic Gastrinoma Causing Zollinger-Ellison Syndrome: A Rare and Challenging Diagnosis|journal=Cancers|volume=4|issue=4|year=2012|pages=130–140|issn=2072-6694|doi=10.3390/cancers4010130}}</ref>
Abdominal [[ultrasound]] may be helpful in the diagnosis of Zollinger-Ellison syndrome caused by [[gastrinoma]].
 
===Other Imaging Studies===
===Other Imaging Studies===
Endoscopic ultrasound and  [[Somatostatin receptor]] scintigraphy (SRS) (octreotide scan)  may be helpful in the diagnosis of Zollinger-Ellison syndrome caused by gastrinoma.<ref name="TangWu2014">{{cite journal|last1=Tang|first1=Shou-jiang|last2=Wu|first2=Ruonan|last3=Bhaijee|first3=Feriyl|title=Zollinger–Ellison Syndrome|journal=Video Journal and Encyclopedia of GI Endoscopy|volume=1|issue=3-4|year=2014|pages=666–668|issn=22120971|doi=10.1016/j.vjgien.2013.06.005}}</ref>
Endoscopic ultrasound and  [[somatostatin receptor]] scintigraphy (SRS) ([[octreotide]] scan)  may be helpful in the diagnosis of Zollinger-Ellison syndrome caused by gastrinoma.
 
===Other Diagnostic Studies===
===Other Diagnostic Studies===
Other diagnostic studies for Zollinger-Ellison syndrome include [[upper endoscopy]], which demonstrates erosive [[esophagitis]], thickened gastric folds, and antral erosions.
Other diagnostic studies for Zollinger-Ellison syndrome include [[upper endoscopy]], which demonstrates erosive [[esophagitis]], thickened gastric folds, and antral erosions.
==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===
Pharmacologic medical therapies for Zollinger-Ellison syndrome include [[proton pump inhibitor]]s, [[H2-receptor antagonist]]s, [[Chemotherapy]], and [[hormonal therapy]].
Pharmacologic medical therapies for Zollinger-Ellison syndrome include [[proton pump inhibitor]]s, [[H2-receptor antagonist]]s, [[chemotherapy]], and [[hormonal therapy]].
 
===Surgery===
===Surgery===
The feasibility of surgery depends on the stage of gastrinoma causing Zollinger-Ellison syndrome at the time of diagnosis. However, all patients diagnosed with Zollinger-Ellison syndrome with no metastasis should be offered surgical exploration and resection.<ref name="pmid10460814">{{cite journal| author=Norton JA, Fraker DL, Alexander HR, Venzon DJ, Doppman JL, Serrano J et al.| title=Surgery to cure the Zollinger-Ellison syndrome. | journal=N Engl J Med | year= 1999 | volume= 341 | issue= 9 | pages= 635-44 | pmid=10460814 | doi=10.1056/NEJM199908263410902 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10460814  }} </ref>
The feasibility of surgery depends on the stage of gastrinoma causing Zollinger-Ellison syndrome at the time of diagnosis. However, all patients diagnosed with Zollinger-Ellison syndrome with no metastasis should be offered surgical exploration and resection.
 
===Primary Prevention===
===Primary Prevention===
Effective measures for the primary prevention of Zollinger-Ellison syndrome include [[genetic testing]], if family history is presents.<ref name="pmid24213231">{{cite journal| author=Harvey A, Pasieka JL, Al-Bisher H, Dixon E| title=Primary hepatic gastrinoma causing zollinger-ellison syndrome: a rare and challenging diagnosis. | journal=Cancers (Basel) | year= 2012 | volume= 4 | issue= 1 | pages= 130-40 | pmid=24213231 | doi=10.3390/cancers4010130 | pmc=PMC3722648 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24213231  }} </ref>
Effective measures for the primary prevention of Zollinger-Ellison syndrome include [[genetic testing]], if family history is positive.
 
===Secondary Prevention===
===Secondary Prevention===
Secondary prevention strategies following Zollinger-Ellison syndrome include surgical resection of [[gastrinoma]] to prevent malignant trasformation and distant [[metastasis]].<ref name="pmid24319020">{{cite journal| author=Epelboym I, Mazeh H| title=Zollinger-Ellison syndrome: classical considerations and current controversies. | journal=Oncologist | year= 2014 | volume= 19 | issue= 1 | pages= 44-50 | pmid=24319020 | doi=10.1634/theoncologist.2013-0369 | pmc=PMC3903066 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24319020  }} </ref>
Secondary prevention strategies following Zollinger-Ellison syndrome include surgical resection of [[gastrinoma]] to prevent malignant trasformation and distant [[metastasis]].
 
==References==
==References==
{{Reflist|2}}
{{Reflist|2}}

Latest revision as of 14:43, 13 March 2019


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2], Aravind Reddy Kothagadi M.B.B.S[3]

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Overview

Patients with Zollinger-Ellison syndrome may experience abdominal pain and diarrhea. The diagnosis is also suspected in patients without symptoms who have severe ulceration of the stomach and small bowel, especially if they fail to respond to treatment. Gastrinomas may occur as single tumors or as multiple, small tumors. About one-half to two-thirds of single gastrinomas are malignant tumors that most commonly spread to the liver and lymph nodes near the pancreas and small bowel. Nearly 25 percent of patients with gastrinomas have multiple tumors as part of a condition called multiple endocrine neoplasia type I (MEN I). MEN I patients have tumors in their pituitary gland and parathyroid glands in addition to tumors of the pancreas. Development of Zollinger-Ellison syndrome is the result of increased levels of gastrin due to an existing gastrinoma in the duodenum or pancreas. Zollinger-Ellison syndrome must be differentiated from gastric antrum syndrome, antral G-cell hyperplasia, peptic ulcer, gastroesophageal reflux disease (GERD), and hypergastrinemia. The incidence of gastrinoma, which can cause Zollinger-Ellison syndrome, is approximately 0.5-2 persons per 100,000 individuals worldwide. Pharmacologic medical therapies for Zollinger-Ellison syndrome include proton pump inhibitors, H2-receptor antagonists, chemotherapy, and hormonal therapy. Effective measures for the primary prevention of Zollinger-Ellison syndrome include genetic testing, if family history presents.

Historical Perspective

In 1955, Zollinger and Ellison published their seminal paper on gastrinomas wherein the Zollinger-Ellison syndrome was first discussed.

Pathophysiology

Development of Zollinger-Ellison syndrome is the result of increased levels of gastrin due to an existing gastrinoma in the duodenum or pancreas.

Causes

The cause of Zollinger-Ellison syndrome has not been identified. However, 25 to 30 percent of gastrinomas, which can cause Zollinger-Ellison syndrome, are caused by multiple endocrine neoplasia type 1 (MEN1).

Differentiating Zollinger-Ellison syndrome from other Diseases

Zollinger-Ellison syndrome must be differentiated from gastric antrum syndrome, antral G-cell hyperplasia, peptic ulcer, gastroesophageal reflux disease (GERD), and hypergastrinemia.

Epidemiology and Demographics

The incidence of gastrinoma, which can cause Zollinger-Ellison syndrome, is approximately 0.05-0.2 per 100,000 individuals worldwide. About 25 to 30 percent of gastrinomas are caused by multiple endocrine neoplasia type 1 (MEN1). Zollinger-Ellison syndrome is a disease that tends to affect the middle-aged adult population. Males are more commonly affected with Zollinger-Ellison syndrome than females.

Natural History, Complications and Prognosis

If left untreated, patients with Zollinger-Ellison syndrome may progress to develop abdominal pain, diarrhea, and heartburn. Common complications of Zollinger-Ellison syndrome include upper gastrointestinal bleeding, anemia, and duodenal ulcer perforation. Prognosis is generally good, and the 5 and 10-year survival rate of patients with Zollinger-Ellison syndrome is approximately 94% and 75%, respectively.

Diagnosis

History and Symptoms

Symptoms of Zollinger-Ellison syndrome include diarrhea, odynophagia, nausea, and hematemesis .

Physical Examination

Common physical examination findings of Zollinger-Ellison syndrome include epigastric tenderness, pallor, and jaundice.

Laboratory Findings

An elevated concentration of fasting serum gastrin level and secretin stimulation test may be helpful in the diagnosis of Zollinger-Ellison syndrome.

Abdominal CT

Abdominal CT scan may be helpful in the diagnosis of Zollinger-Ellison syndrome caused by gastrinoma. Gastrinomas are frequently multiple and often extrapancreatic (90% located in the gastrinoma triangle). Thus, they can be difficult to locate. For this reason, multiphase contrast enhanced thin slice cross-sectional imaging is ideal. Findings on Abdominal CT scan suggestive of gastrinoma include clearly defined, well-enhanced mass.

Abdominal MRI

Abdominal MRI may be helpful in the diagnosis of Zollinger-Ellison syndrome caused by gastrinoma. Findings on abdominal MRI suggestive of Zollinger-Ellison syndrome include solitary lesion or multiple lesions.

Abdominal Ultrasound

Abdominal ultrasound may be helpful in the diagnosis of Zollinger-Ellison syndrome caused by gastrinoma.

Other Imaging Studies

Endoscopic ultrasound and somatostatin receptor scintigraphy (SRS) (octreotide scan) may be helpful in the diagnosis of Zollinger-Ellison syndrome caused by gastrinoma.

Other Diagnostic Studies

Other diagnostic studies for Zollinger-Ellison syndrome include upper endoscopy, which demonstrates erosive esophagitis, thickened gastric folds, and antral erosions.

Treatment

Medical Therapy

Pharmacologic medical therapies for Zollinger-Ellison syndrome include proton pump inhibitors, H2-receptor antagonists, chemotherapy, and hormonal therapy.

Surgery

The feasibility of surgery depends on the stage of gastrinoma causing Zollinger-Ellison syndrome at the time of diagnosis. However, all patients diagnosed with Zollinger-Ellison syndrome with no metastasis should be offered surgical exploration and resection.

Primary Prevention

Effective measures for the primary prevention of Zollinger-Ellison syndrome include genetic testing, if family history is positive.

Secondary Prevention

Secondary prevention strategies following Zollinger-Ellison syndrome include surgical resection of gastrinoma to prevent malignant trasformation and distant metastasis.

References

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