Genetic analysis in young patients with sporadic pituitary macroadenomas:Beside AIP don't forget MEN1 genetic analysis.

T Cuny, Endocrinology, University Hospital of Nancy Brabois, Vandoeuvre-Les-Nancy, France.
European Journal of Endocrinology (Impact Factor: 3.69). 01/2013; DOI: 10.1530/EJE-12-0763
Source: PubMed

ABSTRACT CONTEXT: germline mutations in the AIP gene have been identified in young patients (age ≤ 30 years old) with sporadic pituitary macroadenomas. Otherwise, there are few data concerning the prevalence of MEN1 mutations in such population. OBJECTIVE: We assessed the prevalence of both AIP and MEN1 genetic abnormalities (mutations and large gene deletions) in young patients (age ≤ 30 years old) diagnosed with sporadic and isolated macroadenoma, without hypercalcemia and/or MEN1-associated lesions. DESIGN: The entire coding sequences of AIP and MEN1 were screened for mutations. In cases of negative sequencing screening, multiplex ligation-dependent probe amplification was performed for the detection of large genetic deletions. PATIENTS AND SETTINGS: 174 patients from Endocrinology Departments of 15 French University Hospital Centers were eligible for this study. RESULTS: 21/174(12%) patients had AIP (n=15, 8.6%) or MEN1 (n=6, 3.4%) mutations. In pediatric patients (age ≤ 18 years old), AIP/MEN1 mutation frequency reached nearly 22% (n=10/46). AIPmut and MEN1mut were respectively identified in 8/79 (10.1%) and 1/79 (1.2%) somatotropinoma patients; they each accounted for 4/74 (5.4%) prolactinoma patients with mutations. Half of patients (n=3/6) with gigantism displayed mutations in AIP. Interestingly, 4/12 (33%) patients with non-secreting adenomas bore either AIP or MEN1 mutations, whereas none of the 8 corticotroph-adenomas and a single thyrotropinoma case had mutations. No large gene deletions were observed in sequencing-negative patients. CONCLUSION: mutations in MEN1 can be of significance in young patients with sporadic isolated pituitary macroadenomas, particularly prolactinomas, and together with AIP, we suggest genetic analysis of MEN1 in such population.


Available from: Adrian Francis Daly, Dec 08, 2014
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