Endocrine Abstracts

Introduction: Several genetic syndromes are associated with familial pituitary adenomas. The penetrance of clinical manifestations of these syndromes is not ubiquitous and this might be the reason for the lack of detection of genetic mutations when only one or few genes are studied.

Aim: Clinical characterisation and molecular genetic study of a panel with ten genes involved in formation of pituitary adenomas in familial setting.

Materials and methods: Study included six families (13 patients) with familial pituitary adenomas with no other features of known genetic syndromes. Three families were with the homogeneous type of secretion (acromegaly) and three families with the heterogeneous type (acromegaly/nonactive pituitary adenoma). The study involved five men (38%) and eightt women (62%).

Results: Median age was 55.6 years (40–69 years), the average height for females was 160 cm, for males 170 cm. Most adenomas were GH-producing and non-secreting. The diagnosis of acromegaly was confirmed by hormone testing (GH>2.5 ng/ml< no suppression on OGTT and high IGF1). Maximum GH was 23.9 ng/ml, medium −13.9 (0.42–23.9), IGF1: maximum – 1817, medium – 1517 (439–1817). Minimum size of adenomas was 7 mm, maximum – 17 mm. Tumour extensions were: supra – (three cases, 23%), latero – (two cases, 15%). In most patients, adenomas were extended in more than 2 directions. Genomic DNA from a blood samples of patients (probands) underwent high-throughput sequencing on the Ion Torrent Personal Genome Machine (Life Technologies) using a custom-designed AmpliSeq panel for the sequencing of a panel of genes (MEN1, CDKN1B, PRKAR1A, GNAS, AIP, SDHA, SDHB, SDHC, SDHD, PRKCA, CDKN2C, CDKN2A, POU1F1, PTTG2) but no pathological mutations were detected.

Conclusions: Families with hereditary pituitary adenomas can have tumours with homogenous and heterogeneous types of secretion. We were not able to show any genetic alteration in the group of patients studied.

Disclosure: This work was supported by grant of the President of the Russian Federation MK-5411-2014.7.