Impact of delay in diagnosis in outcomes in MEN1: results from the Dutch MEN1 study group

Rachel S van Leeuwaarde, Bernadette P M van Nesselrooij, Ad R Hermus, Olaf M Dekkers, Wouter W de Herder, Anouk N van der Horst-Schrivers, Madeleine L Drent, Peter H Bisschop, Bas Havekes, Menno R Vriens, Joanne M de Laat, Carolina R C Pieterman, Gerlof D Valk

Research output: Contribution to journalArticleAcademicpeer-review


OBJECTIVE: Identifying a germline mutation in the MEN1 gene in an index case has consequences for a whole family. Eligible family members should be offered genetic counseling and MEN1 mutation testing. Subsequently clinical screening of mutation carriers according to the guidelines should be initiated. We assessed if there is a lag time from MEN1 diagnosis of the index case to MEN1 diagnosis of family members. In addition we determined whether this lag time was associated with an increased morbidity and mortality risk.

DESIGN: A cohort study was performed using the Dutch MEN1 database, including >90% of the Dutch MEN1 population >16 years (n=393).

RESULTS: Fifty-eight MEN1 families were identified of whom 57 index cases and 247 non index cases (n=304). The median lag time in MEN1 diagnosis of family members was 3.5 years (range 0-30). At the time of MEN1 diagnosis 30 (12.1%) non index cases had a duodenopancreatic NET of whom 20% had metastases with a mean lag time of 10.9 years, in comparison with 7.1 years without metastases. Twenty-five (10.1%) non index cases had a pituitary tumor of whom 80% had a microadenoma and 20% a macroadenoma, with mean lag times of 7.2 and 10.6 years respectively. Ninety-five (38.4%) non index cases had a primary hyperparathyroidism(pHPT) with a mean lag time of 9.5 years in comparison with 7 patients without a pHPT with a mean lag time of 3 years (p=0.005). Ten non-index cases died because of a MEN1 related cause that developed in or before the lag time.

CONCLUSION: There is a clinically relevant delay in MEN1 diagnosis in families because of a lag time between the diagnosis of an index case and the rest of the family. More emphasis should be placed on the conduct of proper counseling and genetic testing in all eligible family members.

Original languageEnglish
Pages (from-to)1159-1165
JournalJournal of Clinical Endocrinology and Metabolism
Issue number3
Publication statusPublished - Mar 2016


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