PMID- 19622622
OWN - NLM
STAT- MEDLINE
DCOM- 20091020
LR  - 20211028
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 94
IP  - 10
DP  - 2009 Oct
TI  - Asymptomatic children with multiple endocrine neoplasia type 1 mutations may 
      harbor nonfunctioning pancreatic neuroendocrine tumors.
PG  - 3640-6
LID - 10.1210/jc.2009-0564 [doi]
AB  - CONTEXT: Multiple endocrine neoplasia type 1 (MEN1) is characterized by the 
      occurrence of parathyroid, pituitary, and pancreatic tumors. MEN1, an autosomal 
      dominant disorder, has a high degree of penetrance, such that more than 95% of 
      patients develop clinical manifestations by the fifth decade, although this is 
      lower at approximately 50% by age 20 yr. However, the lower penetrance in the 
      younger group, which is based on detecting hormone-secreting tumors, may be an 
      underestimate because patients may have nonfunctioning tumors and be 
      asymptomatic. OBJECTIVE: The aim of the study was to evaluate the occurrence of 
      nonfunctioning pancreatic neuroendocrine tumors in asymptomatic children with 
      MEN1. PATIENTS: Twelve asymptomatic Northern European children, aged 6 to 16 yr, 
      who were known to have MEN1 mutations were studied. RESULTS: Two asymptomatic 
      children, who were aged 12 and 14 yr, had normal plasma fasting gastrointestinal 
      hormones and were found to have nonfunctioning pancreatic neuroendocrine tumors 
      that were more than 2 cm in size. Surgery and immunostaining revealed that the 
      tumors did not have significant expression of gastrointestinal hormones but did 
      contain chromogranin A and synaptophysin, features consistent with those of 
      nonfunctioning pancreatic neuroendocrine tumors. The tumors had a loss of menin 
      expression. The 14 yr old also had primary hyperparathyroidism and a 
      microprolactinoma, and the 12 yr old had a nonfunctioning pituitary microadenoma. 
      Three other children had primary hyperparathyroidism and a microprolactinoma. 
      CONCLUSION: Nonfunctioning pancreatic neuroendocrine tumors may occur in 
      asymptomatic children with MEN1 mutations, and screening for such 
      enteropancreatic tumors in MEN1 children should be considered earlier than the 
      age of 20 yr, as is currently recommended by the international guidelines.
FAU - Newey, Paul J
AU  - Newey PJ
AD  - Academic Endocrine Unit, Nuffield Department of Clinical Medicine, University of 
      Oxford, Oxford Centre for Diabetes, Endocrinology, and Metabolism (OCDEM), 
      Churchill Hospital, Headington Oxford, OX3 7LJ, United Kingdom.
FAU - Jeyabalan, Jeshmi
AU  - Jeyabalan J
FAU - Walls, Gerard V
AU  - Walls GV
FAU - Christie, Paul T
AU  - Christie PT
FAU - Gleeson, Fergus V
AU  - Gleeson FV
FAU - Gould, Steve
AU  - Gould S
FAU - Johnson, Paul R V
AU  - Johnson PR
FAU - Phillips, Rachel R
AU  - Phillips RR
FAU - Ryan, Fiona J
AU  - Ryan FJ
FAU - Shine, Brian
AU  - Shine B
FAU - Bowl, Michael R
AU  - Bowl MR
FAU - Thakker, Rajesh V
AU  - Thakker RV
LA  - eng
GR  - G9825289/MRC_/Medical Research Council/United Kingdom
GR  - G0501780/MRC_/Medical Research Council/United Kingdom
GR  - 913/DH_/Department of Health/United Kingdom
GR  - G0601423/MRC_/Medical Research Council/United Kingdom
GR  - 913/MSS_/Multiple Sclerosis Society/United Kingdom
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090721
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Chromogranin A)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Synaptophysin)
SB  - IM
MH  - Adenoma/genetics
MH  - Adolescent
MH  - Biomarkers, Tumor/*analysis
MH  - Child
MH  - Chromogranin A/analysis
MH  - Europe
MH  - Female
MH  - Gene Deletion
MH  - Gene Expression Regulation, Neoplastic
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Hyperparathyroidism/genetics
MH  - Immunohistochemistry
MH  - Male
MH  - Multiple Endocrine Neoplasia Type 1/chemistry/*genetics
MH  - *Mutation
MH  - Pancreatic Neoplasms/chemistry/*genetics/pathology/*surgery
MH  - Pedigree
MH  - Pituitary Neoplasms/genetics
MH  - Prolactinoma/genetics
MH  - Proto-Oncogene Proteins/*genetics
MH  - Synaptophysin/analysis
EDAT- 2009/07/23 09:00
MHDA- 2009/10/21 06:00
CRDT- 2009/07/23 09:00
PHST- 2009/07/23 09:00 [entrez]
PHST- 2009/07/23 09:00 [pubmed]
PHST- 2009/10/21 06:00 [medline]
AID - jc.2009-0564 [pii]
AID - 10.1210/jc.2009-0564 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2009 Oct;94(10):3640-6. doi: 10.1210/jc.2009-0564. Epub 
      2009 Jul 21.