The impact of clinical and genetic screenings on the management of the multiple endocrine neoplasia type 1.
OBJECTIVE
To perform clinical and genetic screening for multiple endocrine neoplasia type 1 (MEN1) in patients at the Academic Hospital of the University of São Paulo School of Medicine, and to analyze its impact on clinical management of patients with MEN1.


METHODS
The clinical diagnosis of MEN1 was made in accordance with the Consensus on multiple endocrine neoplasias. Mutation analysis of the entire MEN1 tumor suppressor gene and genetic screening of at-risk family members were performed by direct sequencing. To analyze the implementation of genetic diagnosis, the studied patients were separated into 3 groups: MEN1 index cases (group I), clinically diagnosed MEN1 cases (group II), and genetically diagnosed MEN1 cases (group III).


RESULTS
In total, 154 individuals were clinically and genetically studied. We identified 12 different MEN1 mutations. Fifty-two MEN1 cases were identified: 13 in group I, 28 in group II, and 11 in group III. The mean age in group III (27.0 years) was significantly lower than in groups I (39.5 years) and II (42.4 years; P = 0.03 and P = 0.01, respectively). Patients in groups I and II mostly presented 2 or 3 MEN1-related tumors, while 81.8% of those in group III presented 1 or no MEN1-related tumor. Additionally, in group III, 45.4% of cases were asymptomatic, and no metastasis or death was verified. Surveillance for MEN1 mutations allowed the exclusion of 102 noncarriers, including a case of MEN1 phenocopy.


CONCLUSIONS
Our data supports the benefits of clinical and genetic screening for multiple endocrine neoplasia type 1 in the management of this syndrome.
Lourenço
Delmar Muniz
DM
Unidade de Endocrinologia Genética, LIM-25, Endocrinlologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
Toledo
Rodrigo Almeida
RA
Coutinho
Flavia Lima
FL
Margarido
Leontina Conceição
LC
Siqueira
Sheila Aparecida Coelho
SA
dos Santos
Marcelo Augusto Cortina Gonçalves
MA
Montenegro
Fabio Luiz de Menezes
FL
Machado
Marcel Cerqueira Cesar
MC
Toledo
Sergio Pereira Almeida
SP
D000293:Adolescent; D000328:Adult; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012307:Risk Factors