The clinical and genetic characteristics of patients with gigantism

in Symposium "Perspectives in Endocrinology" - Congresses Highlights 2012: ECE Firenze, ENDO Houston, ESPE Leipzig, SFE Toulouse, IWMEN Liège (2013)

The clinical and genetic characteristics of patients with gigantism

in Abstract book - Aspiring excellence : Pituitary expert forum (2012)

Clinical characterization of cabergoline resistant prolactinomas : a multicenter experience on 92 patients

in ENEA Munich - abstract book (2011, December)

Cyclin dependent kinase inhibitor 1B (CDKN1B) gene mutations in FIPA

in European Neuroendocrine Association - Liège, 22-25 septembre 2010 (2010, September)

Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications.

in Endocrine-Related Cancer (2009), 16(3), 1029-1043

Germline mutations of the aryl hydrocarbon receptor (AHR)-interacting protein (AIP) gene confer a predisposition to pituitary adenomas (PA), usually in the setting of familial isolated PA. To provide ... [more ▼]

Germline mutations of the aryl hydrocarbon receptor (AHR)-interacting protein (AIP) gene confer a predisposition to pituitary adenomas (PA), usually in the setting of familial isolated PA. To provide further insights into the possible role of AIP in pituitary tumour pathogenesis, the expression of AIP and AHR was determined by real-time RT-PCR and/or immunohistochemistry (IHC) in a large series of PA (n=103), including 17 with AIP mutations (AIP(mut)). Variable levels of AIP and AHR transcripts were detected in all PA, with a low AHR expression (P<0.0001 versus AIP). Cytoplasmic AIP and AHR were detected by IHC in 84.0 and 38.6% of PA respectively, and significantly correlated with each other (P=0.006). Nuclear AHR was detected in a minority of PA (19.7%). The highest AIP expression was observed in somatotrophinomas and non-secreting (NS) PA, and multivariate analysis in somatotrophinomas showed a significantly lower AIP immunostaining in invasive versus non-invasive cases (P=0.019). AIP expression was commonly low in other secreting PA. AIP immunostaining was abolished in a minority of AIP(mut) PA, with a frequent loss of cytoplasmic AHR and no evidence of nuclear AHR. In contrast, AIP overexpression in a subset of NS PA could be accompanied by nuclear AHR immunopositivity. We conclude that down-regulation of AIP and AHR may be involved in the aggressiveness of somatotrophinomas. Overall, IHC is a poorly sensitive tool for the screening of AIP mutations. Data obtained on AHR expression suggest that AHR signalling may be differentially affected according to PA phenotype. [less ▲]

Aryl Hydrocarbon Receptor interacting protein (AIP) mutations in a cohort of Brazilian Familial isolated pituitary adenomas : relation to aggressive behaviour

in XIV Simposo Internacinal de Neuroendocrinologia - Endocrinologia and Metabologia - Arquivos Brasileiros de Endocrinologia e Metabologia : Fevereiro 2008, 52, suplemento 1 (2008)

Variable pathological and clinical features of a large Brazilian family harboring a mutation in the aryl hydrocarbon receptor-interacting protein gene

in European Journal of Endocrinology (2007), 157(4), 383-391

Background: Germline aryl hydrocarbon receptor-interacting protein (AIP) mutations occur in 15% of familial isolated pituitary adenoma (FIPA) cases. To date, studies have focused on the identification of ... [more ▼]

Background: Germline aryl hydrocarbon receptor-interacting protein (AIP) mutations occur in 15% of familial isolated pituitary adenoma (FIPA) cases. To date, studies have focused on the identification of such mutations in large international cohorts. Detailed genetic and clinical studies within AIP mutation-positive families have been limited. Aim: To undertake a comprehensive study of a large Brazilian FIPA kindred with an E174 frameshift (E174fs) AIP mutation to assess clinical, hormonal, and radiological features in mutation carriers. Methods: The kindred included 122 subjects across six generations; all underwent clinical examination. Genetic studies were performed to identify E174fs mutation carriers. E174fs-positive subjects underwent magnetic resonance imaging (MRI) and hormonal assessments. Results: Of the ten germline AIP mutation carriers, three had pituitary tumors, while seven were asymptomatic carriers. Three patients with pituitary tumors showed variability in terms of tumor phenotype (two with acromegaly, one with prolactinoma, or mixed prolactin/GH-secreting tumor) and age at diagnosis; both patients with acromegaly had poor responses to octreotide. Tumor AIP immunohistochemistry from the operated patient showed decreased expression when compared with normal tissue. Two adult subjects with normal MRI had elevated IGF-I in the absence of other causes. A 2-year-old child with the E174fs mutation and a normal MRI had premature thelarche, ovarian development, and advanced bone age in the absence of other underlying causes. Conclusions: The penetrance of pituitary tumors in AIP mutation-positive adult subjects was 33.3%, while clinical/hormonal features were variable. The features noted in AIP-mutation carriers in this kindred suggest that clinical characteristics of such carriers may extend beyond pituitary tumors. [less ▲]