The burden of AIP mutations in pituitary adenoma patients from the UK

The burden of AIP mutations in pituitary adenoma patients from the UK F Caimari1, M N Dang1, P Gabrovska1, L C Herna´ndez-Ramı´rez1, K Stals2, A M Bussell2, T Cranston3, N Karavitaki4, A V Kumar5, S Hunter6, T Kearney7, P J Trainer8, I Izatt9, J Bevan10, R Quinton11, J Grieve12, S E Baldeweg13, A B Grossman4, P Morrison14 & M Korbonits1 1Barts and The London School of Medicine, London, UK; 2Royal Devon & Exeter NHS Foundation Trust, Exeter, UK; 3Oxford University Hospitals NHS Trust, Oxford, UK; 4Churchill Hospital, Oxford, UK; 5Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; 6Royal Victoria Hospital, Belfast, UK; 7Salford Royal NHS Foundation Trust, Salford, UK; 8The Christie NHS Foundation Trust, Manchester, UK; 9Guy’s Hospital, London, UK; 10Aberdeen Royal Infirmary, Aberdeen, UK; 11Royal Victoria Infirmary, Newcastle, UK; 12National Hospital for Neurology and Neurosurgery, London, UK; 13University College London Hospital, London, UK; 14Belfast City Hospital, Belfast, UK. Introduction Familial isolated pituitary adenoma (FIPA) and young-onset sporadic pituitary adenoma patients are suggested to be screened for mutations in AIP, a gene described in 2006 and amenable to UK testing since 2008. Methods affected subjects have been tested in Exeter and Oxford genetic laboratories. Data were collected from 120 FIPA-families and 193 sporadic cases with young-onset disease (!30y) from 49 centres in the UK. The Mann–Whitney U test and X2 were used for statistical analysis. Results We have identified 38 AIP pos kindreds (16 families and 22 simplex kindreds), representing 77 affected patients. In the 16 families (13.3% of FIPA-families), out of 211 members tested, 121 were carriers and 55 were affected. Of the 193 young simplex patients (44.5% GH-excess), 22 (11.4%) were AIPpos and 17 unaffected carrier family members were identified. 96 (60%) AIPpos carriers had a founder mutation: p.R304*, 79 subjects and p.F269_H275dup, 17 subjects. In the AIPpos FIPA kindreds, those affected were more frequently males (60.7 vs 41.1%, P!0.001), had younger-onset disease (19y(15–28) vs 32.5y(24–45), P!0.001), and had higher frequency of pituitary apoplexy (12.2 vs 3.8%, PZ0.034) compared to AIPneg FIPA families. There were no differences in tumour size (77.6 vs 72.8% macroadenomas) or extrasellar extension (40 vs 39.8%). Of young sporadic cases, AIPpos patients were more frequently males (81.8 vs 46.8%, PZ0.003), with larger adenomas (100% vs 80.3% macroadenomas, PZ0.043) and extrasellar extension (100 vs 50%, PZ0.004), but no differences in ageof- onset (18(13.5–23) vs 20 (15–25)) or pituitary apoplexy. GH&GH/PRLsecreting adenomas were more frequent in AIPpos compared to AIPneg cases (FIPA: 76.8 vs 31%, P!0.001; sporadic: 95.5 vs 37.9%, P!0.001). Conclusion In the UK population, AIP mutations are found in 13.3% of families and 11.4% of young-onset patients. The two founder mutations identified are responsible for over half of the affected and unaffected carrier cases. DOI: 10.1530/endoabs.38.P311 Society for Endocrinology BES 2015, Edinburgh, UK Endocrine Abstracts Endocrine Abstracts (2015) Vol 38