Multiple endocrine neoplasia syndrome type 1: analysis of data from 102 patients from 43 families in the population of the Russian Federation

BACKGROUND: Multiple endocrine neoplasia syndrome type 1 (MEN-1) is a rare, autosomal dominant disorder resulting from inactivating mutations in the MEN1 gene. It demonstrates high penetrance, with the "classic triad" of manifestations comprising primary hyperparathyroidism (PHPT), gastrointestinal neuroendocrine neoplasms (NEN), and pituitary adenomas. Diagnosis relies on clinical, familial, and genetic criteria. However, significant phenotypic variability and the lack of a clear genotype-phenotype correlation complicate early diagnosis.

AIM: To investigate the clinical-epidemiological, laboratory-instrumental, and genetic characteristics of familial MEN-1 in the Russian population.

MATERIALS AND METHODS: We conducted a single-center, single-stage study (2015–2025) at the Endocrinology Research Centre enrolling 102 genetically confirmed MEN-1 patients from 43 families. Participants were stratified by age at PHPT onset (≤18 years, 19–40 years, and >40 years) and MEN1 mutation type/location. We compared groups using calcium-phosphorus metabolism parameters, disease progression patterns, PHPT surgical outcomes, and genotype-phenotype correlations.

RESULTS: Cohort baseline characteristics (sex, manifestations) were comparable (p>0,05), but we observed significant differences in NEN onset age (p<0,001) and a trend toward higher pituitary adenoma prevalence (p=0,003). Exon 10 mutation were associated with a 7,7-fold increased pituitary adenoma risk (OR=7,7; p=0,006), though mutation type did not predict broader phenotype. Groups did not differ in multiglandular involvement, surgical outcomes, or histopathology (p>0,05).

CONCLUSION: MEN-1 exhibits marked clinical heterogeneity in the Russian population, with exon 10 mutations significantly increasing pituitary adenoma risk. Early-onset PHPT predicts earlier NEN and pituitary adenoma development. These findings support proactive genetic screening and risk-stratified monitoring for MEN-1 families.

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