Endocrine Abstracts

MEN1 germline mutations are identified in 70% of the familial forms of MEN1 and about 10%of the sporadic cases. Little is known about clinical differences between MEN1 with and without identification of MEN1 germline mutation particularly in terms of PA characteristics.

Aim: To compare the clinical features of PA in MEN1 cases with and without germline MEN1 mutation and sporadic cases of PA. Patients and methods: Data were obtained in 39 patients: 22 with MEN1 mutation (Group-I) and 17 sharing MEN1 phenotype but tested negatively for MEN1 mutation (Group-II). All patients presented with PA and primary hyperparathyroidism (PHPT). The genetic diagnosis was performed by direct sequencing of MEN1 exons and intronic boundaries. In 17 MEN1-negative patients large deletions of MEN1 were excluded by MLPA and direct sequencing of CDKN1B gene did not reveal the presence of genetic mutations. Control group (Group-III) included 17 patients with sporadic PA and no evidence of other endocrine tumors (matched by type of secretion and follow-up period to those in Group-II).

Results: In Group-II PA as primary tumor site were more frequent than in Group-I (70% vs 51%, P=0.04). The distribution of the PA type was significantly different between Group-I and Group-II. In Group-II 52% had somatotropinomas, 17% prolactinomas, 17% nonfunctioning adenomas, 11% corticotropinomas. In contrast, in the Group-I 53% consisted prolactinomas and only one patient had acromegaly. The frequency of macroadenomas was not different in Group-I and Group-II (55% vs 59%; P=0.8), but was higher in Group-II patients than in Group-III (59% vs 44%, P=0.041). In secreting PA normalization of pituitary hypersecretion was not significantly different in Group-I and Group-II (50% vs 52%, P=0.48), whereas it was more frequent in Group-III than in Group-II (76% vs 52%, P=0.001). During the whole follow-up 81% patients in Group-I developed gastroenteropancreatic neuroendocrine tumors, whereas in the Group-II such tumors were identified in only 2 patients.

Conclusion: PA in MEN1-phenocopies have different clinical characteristics than those with germline MEN1 mutations. The pituitary tumorogenesis in these patients, especially in those with GH-producing PA and PHPT, might involve mechanisms others than either MEN1 or CDKN1B mutations.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.