Risk factors and causes of death in MEN1 disease. A GTE (Groupe d'Etude des Tumeurs Endocrines) cohort study among 758 patients.
BACKGROUND
The natural history of multiple endocrine neoplasia type 1 (MEN1) is known through single-institution or single-family studies. We aimed to analyze the risk factors and causes of death in a large cohort of MEN1 patients.


METHODS
Overall, 758 symptomatic MEN1 patients were identified through the GTE network (Groupe d'étude des Tumeurs Endocrines), which involves French and Belgian genetics laboratories responsible for MEN1 diagnosis and 80 clinical reference centers. The causes of death were analyzed. A frailty model, including time-dependent variables, was used to assess the impact of each clinical lesion, except for hyperparathyroidism, on survival.


RESULTS
The median follow-up was 6.3 years. Female gender, family history of MEN1, and recent diagnosis were associated with a lower risk of death. Compared with nonaffected patients, those with thymic tumors (hazard ratio [HR] = 4.64, 95% CI = 1.73-12.41), glucagonomas-vipomas-somatostatinomas (HR = 4.29, 95% CI = 1.54-11.93), nonfunctioning pancreatic tumors (HR = 3.43, 95% CI = 1.71-6.88), and gastrinoma (HR = 1.89, 95% CI = 1.09-3.25) had a higher risk of death after adjustment for age, gender, and diagnosis period. The increased risk of death among patients with adrenal tumors was not significant, but three patients died from aggressive adrenal tumors. Pituitary tumors, insulinomas, and bronchial tumors did not increase the risk of death. The proportion of MEN1-related deaths decreased from 76.8 to 71.4% after 1990.


CONCLUSIONS
The prognosis of MEN1 disease has improved since 1980. Thymic tumors and duodenopancreatic tumors, including nonsecreting pancreatic tumors, increased the risk of death. Rare but aggressive adrenal tumors may also cause death. Most deaths were related to MEN1. New recommendations on abdominal and thoracic imaging are required.
Goudet
Pierre
P
Service de Chirurgie Endocrinienne, Centre Hospitalier Universitaire, Dijon, France. pierre.goudet@chu-dijon.fr
Murat
Arnaud
A
Binquet
Christine
C
Cardot-Bauters
Christine
C
Costa
Annie
A
Ruszniewski
Philippe
P
Niccoli
Patricia
P
Ménégaux
Fabrice
F
Chabrier
Georges
G
Borson-Chazot
Françoise
F
Tabarin
Antoine
A
Bouchard
Philippe
P
Delemer
Brigitte
B
Beckers
Alfred
A
Bonithon-Kopp
Claire
C
D000328:Adult; D001530:Belgium / Q000453:epidemiology; D002423:Cause of Death; D016009:Chi-Square Distribution; D003952:Diagnostic Imaging; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000175:diagnosis / Q000401:mortality*; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis