Endocrine Abstracts

Introduction: The genetic causes of development of multiple endocrine neoplasia type 1 (MEN-1) phenocopies remain largely unknown.

Aim of the study: To evaluate the role of genes associated with familial primary hyperparathyroidism (PHPT) in the development of MEN-1 phenocopies with the combination of PHPT and pituitary adenomas (PA).

Materials and methods: 20 patients (19 females and 1 male) were included in the study. All patients had biochemically confirmed PHPT in combination with PA of different types of secretion: 15 GH-secreting, 3 ACTH-secreting, 1 PRL-secreting, 1 non-functioning PA. Median age at the time of inclusion was 61 years [Q25-Q75;min-max:57–66.5;54–79], median age at the time of PHPT diagnosis was 57 years [Q25-Q75;min-max:54–62;51–72], median age at the time of PA diagnosis was 47 years [Q25-Q75;min-max:40.5–57.5;21–61]. Five patients had mild PHPT, 15 – manifest PHPT (though it was difficult to assess the role of PHPT in osteoporosis development due to concomitant menopause and Cushing disease in some cases). Imaging techniques revealed: in 15 patients – solitary parathyroid tumour, in 2 patients – two parathyroid tumours, in 3 patients parathyroid tumours were not visualized. In the majority (n=16) of patients PA was the first manifestation, only in 4 patients PHPT was diagnosed before PA. In all patients no MEN1 mutations were identified by Sanger sequencing, confirming diagnosis of MEN-1 phenocopy. Next-generation sequencing of a custom-designed Ion AmpliSeq^TM panel of genes associated with familial PHPT (MEN1, CASR, CDC73, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2C, CDKN2D) using semiconductor sequencer PGM^TM Ion Torrent (Thermo Fisher Scientific, USA) was performed. ANNOVAR was used for variant annotation.

Results: No pathogenic or likely pathogenic variants in the abovementioned genes were identified.

Conclusion: Mutations in the genes associated with familial PHPT are unlikely to have any role in the development of MEN-1 phenocopies with combination of PHPT and PA.