Analysis of genotype-phenotype correlations and survival outcomes in patients with primary hyperparathyroidism caused by multiple endocrine neoplasia type 1: the experience at a single institution.
OBJECTIVE
To examine the clinical characteristics and survival outcomes of patients with primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia type 1 (MEN1) in relation to the MEN1 gene mutation.


METHODS
The study population included the patients, positive for the MEN1 gene mutation, who underwent parathyroidectomy between 1983 and 2009 at a single tertiary referral center. Manifestations of the syndrome, other tumors and causes of death were retrospectively correlated with the specific types and locations of MEN1 gene mutations.


RESULTS
Thirty-two patients from 19 families were diagnosed as having MEN1 on genetic examinations. Mutations were most common in exons 2, 7 and 10. A phenotypic analysis of the main MEN1 tumor types among the 32 patients revealed that PHPT was the most common (100 %), followed in order by pancreatic neuroendocrine tumors (PNETs) (53 %) and pituitary tumors (38 %). Death due to MEN1-related disease occurred in five patients (16 %), including malignant PNET in three cases (exons 2, 3), pituitary crisis in one case (exon 2) and thymic cancer in one case (large deletion).


CONCLUSIONS
Premature deaths related to MEN1 are due to the development of malignant PNET, pituitary crisis or thymic tumors associated with mutations in exons 2, 3 and a large deletion.
Department of Endocrine Surgery, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. khoriuchi@endos.twmu.ac.jp
Kiyomi
K
Horiuchi
Takahiro
T
Okamoto
Masatoshi
M
Iihara
Toshihiko
T
Tsukada
D000328:Adult; D000368:Aged; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000235:genetics* / Q000401:mortality* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000150:complications* / Q000235:genetics*; D009154:Mutation; D016105:Parathyroidectomy / Q000401:mortality; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins