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.

Purpose: 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.