OR42-5 Pituitary Adenomas due to Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene Mutations: Genotypic-Phenotypic Characteristics, Screening and Prospective Diagnosis

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR42-Cushing's Disease & Non-Functioning Hypothalamic-Pituitary Tumours
Tuesday, June 18, 2013: 9:15 AM-10:45 AM
Presentation Start Time: 10:15 AM
Room 102 (Moscone Center)
Laura C. Hernández-Ramírez*1, Plamena Gabrovska1, Judit Dénes1, Giampaolo Trivellin1, Scott Alexander Akker1, Ashley Grossman2, Mônica R. Gadelha3, Márta Korbonits1 and The International FIPA Consortium1
1Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom, 2Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, United Kingdom, 3Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Mutations in the aryl hydrocarbon receptor interacting protein gene (AIP) play an important role in a subset of inherited pituitary adenomas. We present the clinical characteristics of the largest available cohort of familial isolated pituitary adenomas (FIPA) and AIP mutation-positive (AIPmut) patients.

The AIP gene was analysed in FIPA patients and in young (<30y) sporadic pituitary adenoma patients. The pathogenicity of the detected AIP variants was assessed using in silico prediction programs, as well as considering available data in the scientific literature. Available relatives of AIPmut patients were genetically tested and carriers were clinically screened.

Out of 189 FIPA families, 16.9% (32 families including 96 patients, 104 carriers and 114 at risk subjects with no mutations) carried 17 different AIP mutations. Out of 329 young patients without family history, 9.7% (32 patients, 14 carriers and 11 at risk non-carriers) were identified with 18 different AIP mutations. Out of the 29 mutations 72.4% lead to a truncated or missing protein.

The age of diagnosis was 25.3±12 years [6-62] for familial and 22.1±6 [10-40] for simplex cases. While the simplex cases presented the previously reported predominance of males (64.5% of cases), the gender distribution was more balanced in the familial cases (56.6% of males). The clinical diagnosis corresponded to GH excess (+/- other hormone excesses) in 73.7% of familial and 100% of simplex cases, with a remarkable prevalence of gigantism (39.7% of all AIPmut cases). One fifth of the cases showed plurihormonal and one quarter GH/PRL staining. Three phenocopies were identified in the FIPA families (2 microprolactinomas and one non-functioning pituitary adenoma).

Pituitary apoplexy was diagnosed in 10.1% of familial and 6.25% of simplex cases, noteworthy for a young and somatotropinoma-predominant population.

The clinical screening of AIPmut family members identified 14 cases with pituitary abnormalities representing 24.6% of the 57 studied (hormones/MRI) carriers (age at screening 32.6±18.3yr [1-72]). Five of these prospectively diagnosed patients (4 with large somatotropinomas) have already been operated.

In conclusion, clinical screening of AIP mutation carriers has successfully identified patients with previously not recognised pituitary adenomas leading to earlier treatment. The description of the clinical characteristics of this rare disease has been successfully achieved by world-wide collaboration.

Nothing to Disclose: LCH, PG, JD, GT, SAA, AG, MRG, MK, TI

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Scholarships from the National Council of Science and Technology and the Secretariat of Public Education of the Mexican Government awarded to LCHR. Pfizer-NIHR grant awarded to PG and MK.