CoChat
Sign Up
Cited by 313Neuroendocrine Tumor Research AdvancesPituitary Gland Disorders and TreatmentsGenetic factors in colorectal cancer

Multiple Endocrine Neoplasia Type 1 and Zollinger-Ellison Syndrome: A Prospective Study of 107 Cases and Comparison With 1009 Cases From the Literature

Gibril, Fathia, Schumann, Michael, Pace, Andrea, Jensen, Robert T.·2004·Medicine
DOI 10.1097/01.md.0000112297.72510.32
Open this paper in CoChat — free account

Abstract

In patients with multiple endocrine neoplasia type 1 (MEN1), the most common functional pancreatic endocrine tumor (PET) syndrome is Zollinger-Ellison syndrome (ZES). ZES has been well studied in its sporadic form (that is, without MEN1); however, there are limited data on patients with MEN1 and ZES (MEN1/ZES), and the long-term natural history is largely unknown. To address this issue we report the results of a prospective long-term National Institutes of Health (NIH) study of 107 MEN1/ZES patients and compare our results with those of 1009 MEN1/ZES patients in 278 case reports and small series in the literature. Patients were clinically, radiologically, and biochemically evaluated yearly for all MEN1 manifestations (mean follow-up, 10 yr; range, 0.1-31 yr). Compared with patients from the literature, the NIH MEN1/ZES patients more frequently had pituitary (60%) and adrenal (45%) disease and carcinoid tumors (30%), but had equal frequency of hyperparathyroidism (94%), thyroid disease (6%), or lipomas (5%). Twenty-five percent of both the NIH and the literature patients lacked a family history of MEN1; ZES was the initial clinical manifestation of MEN1 in 40%. ZES onset preceded the diagnosis of hyperparathyroidism in 45%. However, ZES was rarely (8%) the only initial manifestation of MEN1 if careful testing was done. ZES occurred before age 40 years in 50%-60% of the current patients, in contrast to older studies. The diagnosis of ZES is delayed 3-5 years from its onset and is delayed as long as in sporadic ZES cases. Pituitary disease and carcinoid tumors (gastric > bronchial, thymic) are more frequent than generally reported, whereas a second functional PET is uncommon. In patients with MEN1/ZES without a family history of MEN1, the MEN1 manifestations are not as severe. This study shows that MEN1/ZES patients differ in many aspects from those commonly reported in older studies involving few MEN1/ZES patients. In this study we have identified a number of important clinical and laboratory features of MEN1/ZES that were not previously appreciated, which should contribute to earlier diagnosis and improve both short- and long-term management.

Integrity signals

Registry

Crossref · 10.1097/01.md.0000112297.72510.32

Cites

494 of 494 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Associated adrenal lesions, mainly ACAs and uni- or bilateral hyperplasia, occur in 20% to 55% of MEN1 cases.

    “Associated adrenal lesions, mainly ACAs and uni- or bilateral hyperplasia, occur in 20% to 55% of MEN1 cases (45–48).”

    From Adrenocortical carcinoma (2014) · cites this paper as [45]

Cites

Flagged first, then by citations

37 of the 531 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Gibril, F., Schumann, M., Pace, A., & Jensen, R. T.
Affiliations
National Institutes of Health (US)
ORCID
Venue
Medicine
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2004-01
Volume
83
Issue
1
Pages
43-83
ISSN
0025-7974 (ISSN-L)
DOI
10.1097/01.md.0000112297.72510.32
OpenAlex
W2064893457
Cited by
313
References
531
Citations by year
2026: 1 · 2025: 10 · 2024: 7 · 2023: 11 · 2022: 14 · 2021: 15 · 2020: 11 · 2019: 11 · 2018: 15 · 2017: 21 · 2016: 15 · 2015: 20 · 2014: 16 · 2013: 11 · 2012: 23
FWCI
11.26
Type
journal article
Language
en
Open access
closed
Locations
  • Medicine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords
multiple endocrine neoplasia type 1, Zollinger-Ellison syndrome, pancreatic neuroendocrine tumors, hyperparathyroidism, pituitary disorders, adrenal disorders, carcinoid tumor, gastric carcinoid, thymic carcinoid, bronchial carcinoid, delayed diagnosis, natural history (disease), early-onset disease
MeSH terms
Adult, Aged, Diagnosis, Differential, Female, Follow-Up Studies, Genetic Testing, Hormones, Humans, Male, Middle Aged, Prospective Studies, Tomography, X-Ray Computed, Zollinger-Ellison Syndrome, Gastrinoma, Survival Analysis, Treatment Outcome, Age of Onset, Age Distribution, Disease Progression, Multiple Endocrine Neoplasia Type 1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review