Endocrine Abstracts

Introduction: The pathogenesis of pituitary adenomas is incompletely understood. It was recently demonstrated that mutations in AIP, a novel tumor suppressor gene, are causing the familial isolated pituitary adenoma syndrome. Although initial data suggested that AIP mutations are rare in non-familial cases, a recent study demonstrated an increased prevalence in young sporadic macroadenoma patients.

Aim: To perform a systematic screening of AIP mutations in young Romanian sporadic pituitary adenoma patients.

Patients and methods: We studied 40 pituitary adenoma patients from a tertiary referral endocrinology center. Patients were evaluated clinically, biochemically and by pituitary imaging. After informed consent, blood DNA was extracted and all six AIP exons were PCR-amplified and sequenced (Beckman CEQ8000).

Results: The 40 patients included presented the following adenoma types: 9 prolactinomas, 24 GH-secreting, 2 mixed GH-PRL, 1 ACTH-secreting, 4 non-functioning pituitary adenomas (NFPA).

We found several AIP nucleotide single-base substitutions. Bioinformatic analysis was employed to distinguish mutations from known SNPs. One NFPA male patient associating mental retardation (38 yrs. old) presented a heterozygous R16H AIP exon 1 mutation. This has been previously described in familial and sporadic pituitary adenomas, 2 colon cancer patients and 1 control. One male acromegalic patient (18yrs. old at onset), with a large invasive macroadenoma resistant to somatostatin analog therapy, harboured a novel heterozygous exon 6 mutation – R314W. Another acromegalic male patient (29 yrs. old), presenting a macroadenoma resistant to chimeric dopamin-somatostatin analog therapy, harboured a novel heterozygous exon 2 mutation – W73R. Both substitutions affect conserved aminoacids.

Conclusion: We describe two novel putative AIP mutations. In vitro confirmation of their pathogenicity will be needed. Screening of a larger control sample will help exclude that these are rare polymorphisms. Our results suggest that current AIP mutation screening criteria may need to be extended, as evidence is accumulating for their significant prevalence in sporadic adenomas.

Acknowledgments: This work was supported by the Romanian Ministry of Education, Research and Youth (grant numbers CNCSIS TE 227/2010, PNCDI2 41-014/2007).

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.