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See detailDe la génétique des adénomes hypophysaires familiaux
Beckers, Albert ULg; Jaffrain-Rea, M. L.; Daly, Adrian ULg

in Bulletin de l'Académie Nationale de Médecine (2009), 193(7), 1557-1571

Pituitary adenomas were previously thought to be rare. However, a recent cross-sectional study conducted in Liège, Belgium, showed that clinically apparent pituitary adenomas were present in about 1 in ... [more ▼]

Pituitary adenomas were previously thought to be rare. However, a recent cross-sectional study conducted in Liège, Belgium, showed that clinically apparent pituitary adenomas were present in about 1 in 1000 inhabitants, which is 4 to 5 times the previously reported prevalence. Pituitary adenomas are generally sporadic, but some are associated with familial-isolated tumoral syndromes (mainly MEN1 and Carney complex). With the recent characterization of FIPA (Familial Isolated Pituitary Adenomas), familial pituitaru adenomas are now thought to account for 5 % to 8 % of all pituitary tumors. New genetic mechanisms are being identified, improving our understanding of the complex manifestations and sometimes unpredictable outcome of pituitary adenomas. [less ▲]

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See detailThe epidemiology and genetics of pituitary adenomas.
Daly, Adrian ULg; Tichomirowa, M. A.; Beckers, Albert ULg

in Best Practice & Research. Clinical Endocrinology & Metabolism (2009), 23(5), 543-554

According to data derived from autopsy and radiological imaging series, pituitary tumours occur very commonly in the general population; however, most of these tumours are incidental findings with no ... [more ▼]

According to data derived from autopsy and radiological imaging series, pituitary tumours occur very commonly in the general population; however, most of these tumours are incidental findings with no obvious clinical impact. The historical data on the prevalence of pituitary adenomas in the clinical setting are scant and point to such tumours being relatively rare. Recent studies have shown that the prevalence of clinically relevant pituitary adenomas is 3-5 times higher than previously reported, which adds impetus to research into the aetiology of these tumours. Although the majority of pituitary adenomas are sporadic, approximately 5% of all cases occur in a familial setting and over half of these are due to Multiple Endocrine Neoplasia Type 1 (MEN-1) and Carney's Complex (CNC) disorders. Since the late 1990 s, we have described non-MEN1/CNC familial pituitary tumours that include all tumour phenotypes as a condition termed Familial Isolated Pituitary Adenomas (FIPAs). The clinical characteristics of the FIPAs vary from those sporadic pituitary adenomas, as patients with FIPAs have a younger age at diagnosis and larger tumours. About 15% of the FIPA patients have mutations in the aryl hydrocarbon receptor-interacting protein gene (AIP), which indicates that the FIPA may have a diverse genetic pathophysiology. [less ▲]

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See detailExpression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications.
Jaffrain-Rea, M. L.; Angelini, M.; Gargano, D. et al

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 ▲]

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See detailMutaciones de AIP en adenomas hipofisarios familiares y esporadicos: experiencia local y revision de la literatura.
Fajardo-Montanana, C.; Daly, Adrian ULg; Riesgo-Suarez, P. et al

in Endocrinologia y Nutricion (2009), 56(7), 369-377

Clinically relevant pituitary adenomas occur 3-5 times more frequently than previously thought. The majority are isolated cases, but their presentation can be familial in the setting of known syndromes ... [more ▼]

Clinically relevant pituitary adenomas occur 3-5 times more frequently than previously thought. The majority are isolated cases, but their presentation can be familial in the setting of known syndromes such as multiple endocrine neoplasia (MEN)-1 and Carney complex. When 2 or more cases of pituitary adenomas occur in the same family in the absence of the above-mentioned syndromes, a diagnosis of FIPA (familial isolated pituitary adenomas) is made, which accounts for 1-2% of all pituitary adenomas. Mutations of the gene AIP (aryl hydrocarbon receptor-interacting protein) may account for 15% of FIPA families (50% of familial acromegaly), and as such the genetic causes continue to be studied. Also mutations in AIP can be detected in sporadic adenomas among young populations (< 30 years of age). We describe the characteristics of FIPA, detailing the study of a spanish family, in this case AIP mutation negative. Also, the reported findings in sporadic adenomas in the young population are detailed, accompanied by the description of a 19- year old patient with an intronic AIP mutation. Multicenter studies have provided understanding of aspects such as mutations in AIP; however, further studies are necessary to identify other genes involved in FIPA and sporadic pituitary adenomas occurring at a young age. [less ▲]

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See detailFamilial pituitary adenomas.
Tichomirowa, M. A.; Daly, Adrian ULg; Beckers, Albert ULg

in Journal of Internal Medicine (2009), 266(1), 5-18

The majority of pituitary adenomas occur sporadically, however, about 5% of all cases occur in a familial setting, of which over half are due to multiple endocrine neoplasia type 1 (MEN-1) and Carney's ... [more ▼]

The majority of pituitary adenomas occur sporadically, however, about 5% of all cases occur in a familial setting, of which over half are due to multiple endocrine neoplasia type 1 (MEN-1) and Carney's complex (CNC). Since the late 1990s we have described non-MEN1/CNC familial pituitary tumours that include all tumour phenotypes, a condition named familial isolated pituitary adenomas (FIPA). The clinical characteristics of FIPA vary from those of sporadic pituitary adenomas, as patients with FIPA have a younger age at diagnosis and larger tumours. About 15% of FIPA patients have mutations in the aryl hydrocarbon receptor interacting protein gene (AIP), which indicates that FIPA may have a diverse genetic pathophysiology. This review describes the clinical features of familial pituitary adenomas like MEN1, the MEN 1-like syndrome MEN-4, CNC, FIPA, the tumour pathologies found in this setting and the genetic/molecular data that have been recently reported. [less ▲]

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See detailThe Epidemiology of Acromegaly
Beckers, Albert ULg; Daly, Adrian ULg

in John Wass (Ed.) Acromegaly book (2009)

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See detailHigh Incidence of AIP mutations in sporadic pituitary adenomas in young patients with macroadenomas
Tichomirova, M.; Daly, Adrian ULg; Jaffrain-Réa, M. L. et al

in 52 Symposium der Deutschen Gesellschaft für Endokrinologie (2009, March)

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See detailCyclin dependant kinase inhibitor 1B (CDKN1B) gene mutations in familial isolated pituitary adenomas (FIPA) : Analysis in 86 families
Tichomoriva, M.; Barlier, A.; Daly, Adrian ULg et al

in 52 Symposium der Deutschen Gesellschaft für Endokrinologie (2009, March)

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See detailAdénomes hypophysaires familiaux.
Burlacu, M. C.; Tichomirowa, M.; Daly, Adrian ULg et al

in Presse Médicale (2009), 38(1), 112-116

Familial pituitary adenomas are found in multitumoral syndromes such as multiple endocrine neoplasia type 1 (NEM1) and type 4 (NEM4) and the Carney complex (CNC); it remains at present the only known ... [more ▼]

Familial pituitary adenomas are found in multitumoral syndromes such as multiple endocrine neoplasia type 1 (NEM1) and type 4 (NEM4) and the Carney complex (CNC); it remains at present the only known condition in the category of familial isolated pituitary adenomas (FIPA). Familial adenomas account for 3-5% of all pituitary adenomas. Their pathogenesis is known in part: mutations of the menin gene in NEM1 (80%), of the CDKN1B gene in NEM4 (several cases described), of the PRKR1A gene in CNC (50%) and the AIP gene in 15% of FIPA cases (50% of the FIPA cases with a homogeneous somatotropic phenotype). The clinical course of familial adenoma with NEM1 or FIPA is more aggressive than that of sporadic adenoma, with more macroadenomas and more patients diagnosed younger. Familial pituitary adenomas are distinguished from the sporadic forms in their genetic, epidemiologic and clinical characteristics. They require a differentiated management, especially concerning screening. [less ▲]

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See detailTesticular effects of isolated luteinizing hormone deficiency and reversal by long-term human chorionic gonadotropin treatment.
Valdes Socin, Hernan Gonzalo ULg; Salvi, Roberto; Thiry, Albert ULg et al

in Journal of Clinical Endocrinology and Metabolism (2009), 94(1), 3-4

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See detailUpdate on familial pituitary tumors: from multiple endocrine neoplasia type 1 to familial isolated pituitary adenoma.
Daly, Adrian ULg; Tichomirowa, M. A.; Beckers, Albert ULg

in Hormone Research (2009), 71(Suppl 1), 105-111

BACKGROUND: Pituitary adenomas occur in a familial setting in about 5% of all cases and over half of these are due to multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). Since the late ... [more ▼]

BACKGROUND: Pituitary adenomas occur in a familial setting in about 5% of all cases and over half of these are due to multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). Since the late 1990s, we have described non-MEN1/CNC familial pituitary tumors that include all tumor phenotypes and have named this condition 'familial isolated pituitary adenoma' (FIPA). Clinical features of FIPA differ from those of sporadic pituitary adenomas in that patients with FIPA are often younger and have larger tumors at diagnosis. About 15% of FIPA patients have mutations in the aryl hydrocarbon receptor interacting protein gene (AIP), which indicates that FIPA may have a diverse genetic pathophysiology. We review the clinical features of FIPA, the tumor pathologies found in this setting and the genetic/molecular data that have been recently reported. CONCLUSIONS: Clinically relevant pituitary adenomas are more common than previously thought and occur in a familial setting in about 5% of cases overall. Therefore, specific questioning regarding family history of pituitary disease should be part of the workup of all patients with pituitary adenomas, not just those with acromegaly. FIPA is a useful clinical framework to study the features of pituitary adenomas that occur in a familial setting since it encompasses all tumor phenotypes and heterogeneous/homogeneous expression among affected family members. [less ▲]

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See detailLearning from recombinant GH treatment in obesity
Vandeva, S.; Rixhon, M.; Tichomirova, M. A. et al

in Obesity and Metabolism (2009), 5(3/4), 156-166

Obese and untreated growth hormone deficiency (GHD) patients have a number of similar clinical and biological abnormalities. Treatment with recombinant human growth hormone (rhGH) in GHD patients has ... [more ▼]

Obese and untreated growth hormone deficiency (GHD) patients have a number of similar clinical and biological abnormalities. Treatment with recombinant human growth hormone (rhGH) in GHD patients has proven effective in beneficially modulating body composition and certain cardiovascular risk factors, thus leading to the hypothesis that administration of rhGH in obese patients could show similar beneficial results. Hyperinsulinism and increased free fatty acid levels are the main factors causing reduced GH release in the setting of obesity. We reviewed the outcomes of 25 adult and paediatric clinical studies carried out in 1987-2009 that examined the effects of rhGH administration in the obese state. Body composition showed mainly a reduction in visceral abdominal fat, whereas total bodyweight increased or remained unchanged. Effects of rhGH on lipid and carbohydrate metabolic profiles in obese patients were heterogeneous. The increasing burden of obesity on one hand, the absence of definitive medical treatment on the other, give rise to grounds for considering rhGH as a possible therapeutic option if not in the general obese population, at least in patients with higher risk of cardiovascular morbidity and mortality. [less ▲]

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See detailAn analysis of the role of cyclin dependant kinase inhibitor 1B (CDKN1B) gene mutations in 86 families with familial isolated pituitary adenomas (FIPA)
Tichomirova, M. A.; Daly, Adrian ULg; Pujol, Julien ULg et al

in The Endocrine Society's 91st Annual Meeting : 10-13 juin 2009, Washington (2009)

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See detailTSH-secreting pituitary adenoma in a male patient with a novel missense AIP mutation
Fajardo Montanana, C.; Daly, Adrian ULg; Tichomirova, M. A. et al

in The Endocrine Society's 91st Annual Meeting : 10-13 juin 2009, Washington (2009)

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See detailHigh Incidence of AIP mutations in sporadic pituitary adenomas in young patients with macroadenomas
Tichomirova, M. A.; Daly, Adrian ULg; Barlier, A. et al

in The Endocrine Society's 91st Annual Meeting : 10-13 juin 2009, Washington (2009)

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See detailCushing disease : Influence of microsurgery on hormonal balance
Vroonen, Laurent ULg; Martin, Didier ULg; Valdes Socin, Hernan Gonzalo ULg et al

in European Neuroendocrine Association - Workshop : Novel insights in the management of Cushing's syndrome (2009)

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See detailCushing disease : Pituitary microsurgery on hormonal balance
Stevenaert, Achille ULg; Vroonen, Laurent ULg; Perrin, G. et al

in European Neuroendocrine Association - Workshop : Novel insights in the management of Cushing's syndrome (2009)

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See detailThe Genetics in Cushing syndrome
Vandeva, S.; Daly, Adrian ULg; Vroonen, Laurent ULg et al

in European Neuroendocrine Association - Workshop : Novel experimental data on the pituitary and adrenal tumors responsible for Cushing's syndrome (2009)

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See detailCharacterization of prolatinomas resistant to dopaminergic agonists
Vroonen, Laurent ULg; Tamagno, G.; Naves, L. et al

in 19 Meeting of the Belgian Endocrine and Metabolic societies (2009)

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