Endocrine Abstracts

Introduction: Multiple endocrine neoplasia type 1 (MEN 1) is a rare, autosomal dominant disease caused by mutations in the MEN1 gene. The syndrome predisposes an individual to the development of primary hyperparathyroidism (PHPT), gastroenteropancreatic neuroendocrine tumors (GEP-NETs), pituitary adenomas (PA), as well as other endocrine and non-endocrine tumors that usually manifest at a young age. If a patient with the MEN 1 phenotype does not carry mutations in the MEN1 gene, the condition is considered a phenocopy of this syndrome. Comparison of clinical characteristics of mutation-positive and mutation-negative patients may help to identify factors predictive of a positive or negative genetic test.

Materials and methods: The clinical presentations of 85 patients with multiple endocrine neoplasia were analyzed over 5 years. Screening for MEN1 gene mutations was done by Sanger sequencing or by next-generation sequencing using a panel of genes including MEN1.

Results: 42 patients carried MEN1 mutations and 43 patients were mutation-negative. The median age in the phenocopy group was 61 years [48; 65]; in MEN 1 group — 38 years [32; 50] with a predominance of females over males in both groups (82% in non-carriers vs 71% in carriers). The most common combination in the phenocopy group was PA/PHPT (91%) and acromegaly among these patients appeared in 72% cases (versus 11% in MEN1 carriers). In MEN1 mutation carriers the most frequent combination was PHPT/GEP-NETs/PA (57%) and mostly PA secreted prolactin (38%). GEP-NETs developed more frequently in MEN1carriers compared to non-carriers (72% and 16%, respectively, P < 0,01). The prevalence of PHPT in both groups was almost 100% and multiple lesions of parathyroid glands were more common in carriers. Adrenal tumors were equally common in both groups (23% in non-carriers and 26% in carriers).

Conclusion: GEP-NETs in patients with MEN1 phenotypes could possibly predict the presence of a MEN1 mutation. Phenocopies of MEN 1 are quite common and usually occur in older patients, with a female predominance; the most common combination of tumors in this group is PHPT/PA (GH secreting).The etiology of the combination of several endocrine MEN 1-associated tumors in such patients remains unknown. As possible causes, mutations in other, not yet established, genes, epigenetic changes, as well as a random combination of several tumors in one patient can be considered.