PMID- 30254610
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 9
DP  - 2018
TI  - The Importance of an Early and Accurate MEN1 Diagnosis.
PG  - 533
LID - 10.3389/fendo.2018.00533 [doi]
LID - 533
AB  - Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant inherited 
      condition, causing significant morbidity, and a reduction of life expectancy. A 
      timely and accurate diagnosis of MEN1 is paramount to improve disease outcomes. 
      This enables early identification of tumor manifestations allowing timely 
      treatment for reducing morbidity and improving survival. Current management of 
      MEN1 poses two challenges regarding the MEN1 diagnosis: diagnostic delay and the 
      issue of phenocopies. A delay in diagnosis can be caused by a delay in 
      identifying the index case, and by a delay in identifying affected family members 
      of an index case. At present, lag time between diagnosis of MEN1 in index cases 
      and genetic testing of family members was estimated to be 3.5 years. A subsequent 
      delay in diagnosing affected family members was demonstrated to cause potential 
      harm. Non-index cases have been found to develop clinically relevant tumor 
      manifestations during the lag times. Centralized care, monitoring of patients 
      outcomes on a national level and thereby improving awareness of physicians 
      treating MEN1 patients, will contribute to improved care. The second challenge 
      relates to "phenocopies." Phenocopies refers to the 5-25% of clinically diagnosed 
      patients with MEN1in whom no mutation can be found. Up to now, the clinical 
      diagnosis of MEN1 is defined as the simultaneous presence of at least two of the 
      three characteristic tumors (pituitary, parathyroids, or pancreatic islets). 
      These clinically diagnosed patients undergo intensive follow up. Recent insights, 
      however, challenge the validity of this clinical criterion. The most common 
      mutation-negative MEN1 phenotype is the combination of primary 
      hyperparathyroidism and a pituitary adenoma. This phenotype might also be caused 
      by mutations in the CDKN1B gene, causing the recently described MEN4 syndrome. 
      Moreover, primary hyperparathyroidism and pituitary adenoma are relatively common 
      in the general population. Limiting follow-up in patients with a sporadic 
      co-occurrence of pHPT and PIT could reduce exposure to radiation from imaging, 
      healthcare costs and anxiety.
FAU - de Laat, Joanne M
AU  - de Laat JM
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, 
      Netherlands.
FAU - van Leeuwaarde, Rachel S
AU  - van Leeuwaarde RS
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, 
      Netherlands.
FAU - Valk, Gerlof D
AU  - Valk GD
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, 
      Netherlands.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20180911
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
PMC - PMC6141626
OTO - NOTNLM
OT  - MEN1
OT  - delayed diagnosis
OT  - diagnosis
OT  - epidemiology
OT  - genetic testing
EDAT- 2018/09/27 06:00
MHDA- 2018/09/27 06:01
PMCR- 2018/01/01
CRDT- 2018/09/27 06:00
PHST- 2018/04/18 00:00 [received]
PHST- 2018/08/22 00:00 [accepted]
PHST- 2018/09/27 06:00 [entrez]
PHST- 2018/09/27 06:00 [pubmed]
PHST- 2018/09/27 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2018.00533 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2018 Sep 11;9:533. doi: 10.3389/fendo.2018.00533. 
      eCollection 2018.