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

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

Pituitary MRI characteristics in 297 acromegaly patients based on T2-weighted sequences.

Context: Responses of GH-secreting adenomas to multimodal management of acromegaly varies widely between patients. Understanding the behavioral patterns of GH-secreting adenomas by identifying predictive factors of their evolution is a research priority. Objective: To clarify the relationship between adenoma T2-weighted signal on diagnostic MRI in acromegaly and clinical and biological features at diagnosis. Design: International, multicenter, retrospective analysis. Setting: 10 endocrine tertiary referral centers. Patients: 297 acromegalic recently diagnosed patients with available diagnostic MRI evaluations were included in the study. Main outcome measure: Clinical, biochemical characteristics and MRI signal findings. Results: T2-hypointense adenomas represented 52.9% of the series, were smaller than their T2-hyper- and isointense counterparts (p<0.0001), were associated with higher IGF1 levels (p=0.0001), invaded the cavernous sinus less frequently (p=0.0002) and rarely caused optic chiasm compression (p<0.0001). Acromegalic men tended to be younger at diagnosis than women (p=0.067) and presented higher IGF1 values (p=0.01). Although in total, adenomas had a predominantly inferior extension in 45.8% of cases, in men this was more frequent (p<0.0001), whereas in women optic chiasm compression of macroadenomas occurred more often (p=0.0067). Most adenomas (45.1%) measured between 11-20mm in maximal diameter and bigger adenomas were diagnosed at younger ages (p=0.0001). Conclusions: T2-weighted signal differentiates GH-secreting adenomas into subgroups with particular behaviors. This raises the question of whether T2-weighted signal could represent a factor in the classification of acromegalic patients in future studies

Acromegaly at diagnosis in 3173 patients from the Liege Acromegaly Survey (LAS) database.

Acromegaly is a rare disorder caused by chronic growth hormone (GH) hypersecretion. While diagnostic and therapeutic methods have advanced, little information exists on trends in acromegaly characteristics over time. The Liege Acromegaly Survey (LAS) database, a relational database, is designed to assess the profile of acromegaly patients at diagnosis and during long-term follow-up at multiple treatment centers. The study population consisted of 3173 acromegaly patients from ten countries; 54.5% were female. Males were significantly younger at diagnosis than females (43.5 vs. 46.4 years; p3100 patients is the largest international acromegaly database and shows clinically relevant trends in the characteristics of acromegaly at diagnosis