Endocrine Abstracts

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease caused by mutations in the MEN1 gene (a tumor supressor gene) leading to the development of endocrine and non-endocrine tumours with variable penetrance.

The most frequent features are primary hyperparathyroidism, duodeno pancreatic endocrine tumours and pituitary adenomas.

Aim of the work: The aim of this retrospective study was to establish the prevalence and characteristics of multiple endocrine neoplasia type 1 patients followed at the University Hospital of Liege these last 35 years.

Methods: We studied the data of 50 MEN1 patients from 15 families, followed or diagnosed in our center between 1985 and 2020. We collected data regarding the mutations, the types of tumours, their clinical presentation and the treatments administered.

Results: In our MEN1 series, 41 (82%) patients were MEN1 mutation positive, and 9 (18%) were MEN1 mutation negative. The mutation-negative cases were diagnosed at an older age (59 vs 33 years, P=0.018) and had only two of the three major conditions associated with MEN1. None of them had CDKN1B mutation. Primary hyperparathyroidism was the most frequent manifestation and occurred in 38 of 50 patient (81%). It was the first clinical manifestation of the disease in 17 patients (37.8%). Ultrasonography was able to locate abnormal parathyroid glands in 76% of cases. Primary hyperparathyroid was most commonly induced by multiglandular hyperplasia (approximately 64%). Eighty percent of patients had damage of the target organs, mainly osteopenia/osteoporosis. Surgery was performed in 27 patients (71%) with 11 relapses (44%). The second most frequent lesion was duodeno-pancreatic involvement (70% of cases, n=35) predominantly manifesting as nonfunctional tumours (56 %). Pituitary adenomas were found in 23 patients (52%). Fifty percent of these tumors were macroadenomas. There were 12 prolactinomas, 6 nonsecreting tumors, 2 gonadotrophinomas, 1 Somatotrophinoma, 1 somatomammotrope adenoma and 1 with insufficient data. Adrenal enlargement was reported in 7 patients (17%) with hormonal hypersecretion in 1 case (primary hyperaldosteronism). Six patients developed ‘carcinoid’ tumours: 2 bronchial, 2 thymic and 2 gastric.

Conclusions: In our series, 9 patients (18%) were MEN1 mutation negative. The patients with MEN1-associated tumors but without MEN1 mutations may represent phenocopies or have mutations involving other genes. The tumors encountered in multiple endocrine neoplasia type 1 differ from their sporadic forms in many ways. Primary hyperparathyroidism occurs earlier and is associated with pluriglandular hyperplasia in about 60 % of cases. Ultrasonography was able to locate abnormal parathyroid glands in 76% of cases while the reported sensitivity of conventional ultrasonography for localization ranges from 49% to 89%. In our MEN1 series, the risk of recurrence of hyperparathyroidism was the same regardless of the type of surgery (subtotal vs adenomectomy), the histological nature (adenoma vs hyperplasia) and the finding of MEN1 mutations. Pituitary adenomas were generally larger than their sporadic forms and were frequently prolactinomas. They had developped at a younger age when compared to sporadic pituitary adenomas. Early diagnosis of MEN1 syndrome is essential in order to set up specific monitoring and early intervention, limiting the risk of abnormal hormone secretion and malignant progression.