Endocrine Abstracts

Introduction: Around 15–20% of patients suffering from familial isolated pituitary adenoma (FIPA) possess heterozygous germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. AIP carriers are predisposed to pituitary adenomas with a penetrance of approximately 20%. No other tumours have been observed in subjects with AIP mutations, hence the name “isolated”. AIP is acting as a tumour suppressor gene in the pituitary and loss of heterozygosity (LOH) has been identified in most pituitary adenoma samples from AIP mutation-positive patients. The purpose of this study was to investigate whether LOH played a role in a patient with AIP mutation with an incidental finding of a glioma.

Case report: A 52 y old male was screened for AIP mutation as his brother, who suffers from young-onset, somatostatin analogue resistant acromegaly, was found to be a carrier (p.R304*). The patient underwent clinical screening: while no abnormalities were found in his pituitary hormones and his pituitary was normal size on MRI, an incidental finding of a glioma was identified in the right frontal lobe. Following four years of observation, while he was asymptomatic, he was operated due to gradual increase of tumour size.

Methods: DNA was extracted from blood and from the glioma sample carefully avoiding normal tissue. PCR amplification and sequencing of the region (exon 6) possessing the AIP mutation was performed.

Results: Sequence analysis revealed a heterozygous state both in the blood as well as in the glioma-derived DNA, indicating lack of “loss of heterozygosity” in the glioma.

Conclusion: The sequencing result supports, although does not prove, that the AIP mutation is unlikely to play a role in the pathogenesis of the glioma. This supports clinical observations and similar studies in meningioma (Guaraldi, Pituitary, 2012), showing that AIP mutations do not predispose to tumours outside the pituitary gland.