Patients with multiple endocrine neoplasia type 1 with gastrinomas have an increased risk of severe esophageal disease including stricture and the premalignant condition, Barrett's esophagus.
BACKGROUND
Multiple endocrine neoplasia type 1 (MEN1) patients frequently develop Zollinger-Ellison syndrome (MEN1/ZES). Although esophageal reflux symptoms are common in these patients, little is known about long-term occurrence of severe peptic esophageal disease including strictures and Barrett's esophagus (BE).


OBJECTIVE
The objective of the study was to prospectively analyze the frequency of severe peptic esophageal disease in ZES patients with and without MEN1.


METHODS
The study was conducted at a tertiary care research center.


METHODS
Two hundred ninety-five patients (80 = MEN1/ZES, 215 = sporadic ZES) participated in a prospective study.


METHODS
Assessment of MEN1, acid hypersecretion, upper gastrointestinal endoscopy/biopsies, and tumor status were measured initially and at each follow-up. Esophageal manometry was performed in 89 patients. Frequency and type of esophageal disease were correlated with clinical/laboratory/tumoral features of ZES/MEN1.


RESULTS
In MEN1/ZES patients, esophageal stricture was 3-fold higher, BE 5-fold higher, and dysplasia 8-fold higher, and one patient died of esophageal adenocarcinoma. Esophageal symptoms were more frequent or severe in MEN1/ZES, but known risk factors for severe esophageal disease and ZES-specific features did not differ between MEN1/ZES and sporadic ZES. In MEN1/ZES, the onset of ZES was 10 yr earlier, and H2-antagonists were used longer and at lower doses. MEN1/ZES patients with esophageal disease differed from those without in that ZES diagnosis was delayed longer, esophageal symptoms were more frequent or severe, hiatal hernias were more frequent, esophagitis or pyloric scarring was more common, basal acid output was higher, and hyperparathyroidism was underdiagnosed.


CONCLUSIONS
This study shows that MEN1/ZES patients have a higher incidence of severe esophageal disease including the premalignant condition BE and identifies factors important for their pathogenesis that need to be incorporated into their long-term treatment.
Hoffmann
K Martin
KM
Digestive National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases/Digestive Diseases Branch, Bethesda, Maryland 20892-1804, USA.
Gibril
Fathia
F
Entsuah
Laurence K
LK
Serrano
Jose
J
Jensen
Robert T
RT
D000328:Adult; D001471:Barrett Esophagus / Q000453:epidemiology* / Q000209:etiology*; D004935:Esophageal Diseases / Q000453:epidemiology* / Q000209:etiology*; D049630:Esophageal Sphincter, Lower / Q000503:physiopathology; D004940:Esophageal Stenosis / Q000453:epidemiology* / Q000209:etiology*; D004945:Esophagoscopy; D005260:Female; D005745:Gastric Acidity Determination; D015408:Gastrinoma / Q000150:complications*; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D008297:Male; D018761:Multiple Endocrine Neoplasia Type 1 / Q000150:complications*; D011446:Prospective Studies; D012306:Risk; D012737:Sex Factors; D015043:Zollinger-Ellison Syndrome / Q000150:complications
D006635:Histamine H2 Antagonists