PMID- 11134142
OWN - NLM
STAT- MEDLINE
DCOM- 20010202
LR  - 20041117
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 85
IP  - 12
DP  - 2000 Dec
TI  - Pituitary macroadenoma in a 5-year-old: an early expression of multiple endocrine 
      neoplasia type 1.
PG  - 4776-80
AB  - Multiple endocrine neoplasia type 1 (MEN 1) is associated with parathyroid, 
      enteropancreatic, pituitary, and other tumors. The MEN1 gene, a tumor suppressor, 
      is located on chromosome 11. Affected individuals inherit a mutated MEN1 allele, 
      and tumorigenesis in specific tissues follows inactivation of the remaining MEN1 
      allele. MEN 1-associated endocrine tumors usually become clinically evident in 
      late adolescence or young adulthood, as high levels of PTH, gastrin, or PRL. 
      Because each of these tumors can usually be controlled with medications and/or 
      surgery, MEN 1 has been regarded mainly as a treatable endocrinopathy of adults. 
      Unlike in MEN 2, early testing of children in MEN 1 families is not recommended. 
      We report a 2.3-cm pituitary macroadenoma in a 5-yr-old boy with familial MEN 1. 
      He presented with growth acceleration, acromegaloid features, and 
      hyperprolactinemia. We tested systematically to see whether his pituitary tumor 
      had causes similar to or different from a typical MEN 1 tumor. Germ line DNA of 
      the propositus and his affected relatives revealed a heterozygous point mutation 
      in the MEN1 gene, which leads to a His139Asp (H139D) amino acid substitution. The 
      patient had no other detectable germ-line mutations on either MEN1 allele. DNA 
      sequencing and fluorescent in situ hybridization with a MEN1 genomic DNA sequence 
      probe each demonstrated one copy of the MEN1 gene to be deleted in the pituitary 
      tumor and not in normal DNA, proving MEN1 "second hit" as a tumor cause. Gsalpha 
      mutation, common in nonhereditary GH-producing tumors, was not detected in this 
      tumor. We conclude that this pituitary macroadenoma showed molecular genetic 
      features of a typical MEN 1-associated tumor. This patient represents the 
      earliest presentation of any morbid endocrine tumor in MEN 1. A better 
      understanding of early onset MEN 1 disease is needed to formulate recommendations 
      for early MEN 1 genetic testing.
FAU - Stratakis, C A
AU  - Stratakis CA
AD  - Developmental Endocrinology Branch, National Institute of Child Health and Human 
      Development, National Institute of Health, Bethesda, MD 20892-1862, USA. 
      stratakc@cc1.nichd.nih.gov
FAU - Schussheim, D H
AU  - Schussheim DH
FAU - Freedman, S M
AU  - Freedman SM
FAU - Keil, M F
AU  - Keil MF
FAU - Pack, S D
AU  - Pack SD
FAU - Agarwal, S K
AU  - Agarwal SK
FAU - Skarulis, M C
AU  - Skarulis MC
FAU - Weil, R J
AU  - Weil RJ
FAU - Lubensky, I A
AU  - Lubensky IA
FAU - Zhuang, Z
AU  - Zhuang Z
FAU - Oldfield, E H
AU  - Oldfield EH
FAU - Marx, S J
AU  - Marx SJ
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adenoma/*genetics/pathology
MH  - Alleles
MH  - Child, Preschool
MH  - DNA/genetics/isolation & purification
MH  - DNA Mutational Analysis
MH  - Gene Deletion
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/pathology
MH  - Pituitary Neoplasms/*genetics/pathology
MH  - Point Mutation/genetics
EDAT- 2001/01/03 11:00
MHDA- 2001/03/03 10:01
CRDT- 2001/01/03 11:00
PHST- 2001/01/03 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2001/01/03 11:00 [entrez]
AID - 10.1210/jcem.85.12.7064 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2000 Dec;85(12):4776-80. doi: 10.1210/jcem.85.12.7064.