References of "Daly, Adrian"
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See detailManagement of acromegaly
Vasilev, Vladimir ULg; Daly, Adrian ULg; Zacharieva, Sabina et al

in F1000 Medecine Reports (2010), 2(54),

Acromegaly is caused by hypersecretion of growth hormone and resultant overproduction of insulinlike growth factor-1 and is associated with increased mortality and morbidity. Successful treatment ... [more ▼]

Acromegaly is caused by hypersecretion of growth hormone and resultant overproduction of insulinlike growth factor-1 and is associated with increased mortality and morbidity. Successful treatment modalities have been developed and are used in a multistep approach allowing normal life expectancy as well as improved quality of life in an increasing number of patients. [less ▲]

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See detailThe genetics of pituitary adenomas
Vandeva-Kalvacheva, Silvia ULg; Jaffrain-Rea, M. L.; Daly, Adrian ULg et al

in Best Practice & Research. Clinical Endocrinology & Metabolism (2010), 24(3), 461-76

Pituitary adenomas are one of the most frequent intracranial tumors with a prevalence of clinically-apparent tumors close to 1:1000 of the general population. They are clinically significant beause of ... [more ▼]

Pituitary adenomas are one of the most frequent intracranial tumors with a prevalence of clinically-apparent tumors close to 1:1000 of the general population. They are clinically significant beause of hormone overproduction and/or tumor mass effects in addition to the need for neurosurgery medical therapies and radiotherapy. The majority of pituitary adenomas have a sporadic origin with recognized genetic mutations seldom being found; somatotropinomas are an exception, presenting frequent somatic GNAS mutations. In this and other phenotypes, tumorigenesis could possibly be explained by altered function of genes implicated in cell cycle regulation, growth factors or their receptors, cell-signaling pathways, specific hormonal factors or other molecules with still unclear mechanisms of action. Genetic changes, such as allelic loss or gene amplification, and epigenetic changes, usually by promoter methylation, have been implicated in abnormal gene expression, but alternative mechanisms may be present. Familial cases of pituitary adenomas represent 5% of all pituitary tumors. MEN1 mutations cause multiple endocrine neoplasia type 1 (MEN1), while the Carney complex (CNC) is charcaterized by mutations in the protein kinase A regulatory subunit-1alpha (PRKAR1A) gene or changes in a locus at 2p16. Recently, a MEN1-like conditions, MEN4, was found to be related to mutations in the CDKN1B gene. The clinical entity of familialt isolated pituitary adenomas (FIPA) is characterized by genetic defects in the aryl hydrocarbon receptor interacting protein (AIP) gene in about 15% of all kindreds and 50% of homogenous somatotropinoma families. Identification of familial cases of pituitary adenomas is important as these tumors may be more aggressive than their sporadic counterparts. [less ▲]

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See detailHyperplasia-adenoma sequence in pituitary tumorigenesis related to AIP mutation
Daly, Adrian ULg; Beckers, Albert ULg

in ENDO 2010 : The 92nd Annual Meeting (2010, June)

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See detailCharacterization of prolatinomas resistant to dopaminergic agonists
Vroonen, Laurent ULg; Daly, Adrian ULg; Beckers, Albert ULg

in ENDO 2010 : The 92nd Annual Meeting (2010, June)

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See detailThe role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes.
Stratakis, C. A.; Tichomirowa, M. A.; Boikos, S. et al

in Clinical Genetics (2010)

The role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes. The prevalence of ... [more ▼]

The role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes. The prevalence of germline mutations in MEN1, AIP, PRKAR1A, CDKN1B and CDKN2CI is unknown among pediatric patients with pituitary adenomas (PA). In this study, we screened children with PA for mutations in these genes; somatic GNAS mutations were also studied in a limited number of growth hormone (GH) or prolactin (PRL)-secreting PA. We studied 74 and 6 patients with either isolated Cushing disease (CD) or GH- or PRL-secreting PA, respectively. We also screened four pediatric patients with CD, and four with GH/PRL-secreting tumors who had some syndromic features. There was one AIP mutation (p.Lys103Arg) among 74 CD patients. Two MEN1 mutations that occurred in patients with recurrent or difficult-to-treat disease were found among patients with CD. There was one MEN1 and three AIP mutations (p.Gln307ProfsX104, p.Pro114fsX, p.Lys241X) among pediatric patients with isolated GH- or PRL-secreting PA and one additional MEN1 mutation in a patient with positive family history. There were no mutations in the PRKAR1A, CDKN1B, CDKN2C or GNAS genes. Thus, germline AIP or MEN1 gene mutations are frequent among pediatric patients with GH- or PRL-secreting PA but are significantly rarer in pediatric CD; PRKAR1A mutations are not present in PA outside of Carney complex. [less ▲]

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See detailScreening for AIP mutations in young patients with pituitary macroadenomas
Jaffrain-Réa, M. L.; Tichomirova, M.; Angelini, M. et al

in 5° Incontro Italiano Malattie Ipotalamo Ipofisarie (2010, January)

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See detailPrevalence of double pituitary adenomas in a surgical series: Clinical, histological and genetic features.
Magri, F.; Villa, C.; Locatelli, D. et al

in Journal of Endocrinological Investigation (2010), 33(5), 325-31

BACKGROUND: The term double pituitary adenomas (DPA) is usually referred to those rare lesions showing two distinct cellular components. Genetic background may sustain the proliferation of more than one ... [more ▼]

BACKGROUND: The term double pituitary adenomas (DPA) is usually referred to those rare lesions showing two distinct cellular components. Genetic background may sustain the proliferation of more than one cell at the same time but no information is available on the presence of aip mutations in these patients. AIM: We report the prevalence and the endocrinological, neuroradiological, histopathological and genetic features of DPA detected in a large surgical series. The contribution of pituitary transcription factor immunostains in DPA was also evaluated. SUBJECTS AND METHODS: One-hundred-forty-four patients undergoing surgery for tumors of the sellar region were evaluated. Histopathology, immunohistochemistry and the mutational analysis for the entire coding region of the AIP and MEN1 genes were performed. RESULTS: One-hundred-seventeen patients out of 144 had a pituitary adenoma. DPA was found in 3 (2.6%) out of 117 patients with pituitary adenoma. Immunohistochemistry and transcription factors analysis demonstrated two not yet described histotype associations in DPA. The coexistence of somatotroph-lactotroph and silent mammosomatotroph histotype in 1 case and the coexistence of sparsely granulated lactotroph and null cell adenomas in the remaining two cases were first identified. Sequencing data for the coding region of the aip and the menin gene resulted in wild type sequences in all patients with DPA. CONCLUSIONS: The prevalence of DPA observed in our unselected surgical series is not negligible (2.6%). Furthermore, the evaluation of the treatment outcome would suggest that the clinical management of DPAs requires a careful diagnostic approach and follow- up. [less ▲]

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See detailFamilial pituitary adenomas
vandeva, s; Vasilev, V.; Vroonen, Laurent ULg et al

in Annales d'Endocrinologie (2010), 71

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See detailClinical characteristics and therapeutic responses in patients with Germ-line AIP mutations and pituitary adenomas : An international collaborative study
Daly, Adrian ULg; Tichomirowa, Maria A.; Petrossians, Patrick ULg et al

in Journal of Clinical Endocrinology and Metabolism (2010), 95(11),

Context: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features ... [more ▼]

Context: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. <br />Objective: The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. <br />Design: This study was an international, multicenter, retrospective case collection/database analysis. <br />Setting: The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. <br />Patients: Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. <br />Results: The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy. <br />Conclusions: AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility. [less ▲]

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See detailYoung patients with sporadic pituitary macroadenomas as target population of AIP mutation screening
Tichomirova, M.; Daly, Adrian ULg; Beckers, Albert ULg

in 12th European Congress of Endocrinology - ICE 2010 (2010)

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See detailThe ratio of PTH as measured by third and second generation assays as a marker for parathyroid carcinoma
Cavalier, Etienne ULg; Daly, Adrian ULg; Chapelle, Jean-Paul ULg et al

in 12th European Congress of Endocrinology - ICE 2010 (2010)

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See detailGenetic Factors in the Development of Pituitary Adenomas.
Vandeva, S.; Tichomirowa, M. A.; Zacharieva, S. et al

in Endocrine Development (2010), 17

Pituitary adenomas are one of the most frequent intracranial tumors. Usually, they are benign but are of great clinical significance because of tumor compression syndrome and hormone overproduction. The ... [more ▼]

Pituitary adenomas are one of the most frequent intracranial tumors. Usually, they are benign but are of great clinical significance because of tumor compression syndrome and hormone overproduction. The interest in this pathology is increasing, particularly after some recent reports on their prevalence that proved to be 3-5 times more than previously estimated. Pituitary tumors arise in a sporadic setting and rarely as part of hereditary genetic syndromes. Such rare hereditary conditions like MEN1, Carney complex and McCune-Albright syndrome give significant insight into pituitary tumorigenesis. Newer genes associated pituitary tumor development include CDKN1B (MEN4) and AIP, the latter of which is involved in the pathophysiology of 15% of FIPA kindreds. The number of genes involved in pituitary tumorigenesis is progressively increasing and the possible mechanisms of action include signal transduction pathways, cell cycle regulators, growth factors, chromosome instability and others. Nevertheless, in the majority of sporadic adenomas, the primary genetic defect remains unknown. Furthermore, there is not a well established relationship between the genotype and its influence on the protein expression, ligand-receptor interaction, tumor growth or hormone hyperproduction. Further studies should evaluate the clinical significance of genetic alterations and their implications for existing and new therapeutic options. [less ▲]

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See detailAggressive pituitary adenomas occurring in young patients in a large Polynesian kindred with a germline R271W mutation in the AIP gene.
Jennings, J. E.; Georgitsi, M.; Holdaway, I. et al

in European Journal of Endocrinology (2009), 161(5), 799-804

OBJECTIVE: Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) were recently shown to confer a pituitary adenoma predisposition in patients with familial isolated pituitary adenomas (FIPA ... [more ▼]

OBJECTIVE: Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) were recently shown to confer a pituitary adenoma predisposition in patients with familial isolated pituitary adenomas (FIPA). We report a large Samoan FIPA kindred from Australia/New Zealand with an R271W mutation that was associated with aggressive pituitary tumors. DESIGN AND METHODS: Case series with germline screening of AIP and haplotype analyses among R271W families. RESULTS: This previously unreported kindred consisted of three affected individuals that either presented with or had first symptoms of a pituitary macroadenoma in late childhood or adolescence. The index case, a 15-year-old male with incipient gigantism and his maternal aunt, had somatotropinomas, and the maternal uncle of the index case had a prolactinoma. All tumors were large (15, 40, and 60 mm maximum diameter) and two required transcranial surgery and radiotherapy. All three affected subjects and ten other unaffected relatives were found to be positive for a germline R271W AIP mutation. Comparison of the single nucleotide polymorphism patterns among this family and two previously reported European FIPA families with the same R271W mutation demonstrated no common ancestry. CONCLUSIONS: This kindred exemplifies the aggressive features of pituitary adenomas associated with AIP mutations, while genetic analyses among three R271W FIPA families indicate that R271W represents a mutational hotspot that should be studied further in functional studies. [less ▲]

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See detailTumor ZAC1 expression is associated with the response to somatostatin analog therapy in patients with acromegaly.
Theodoropoulou, Marily; Tichomirowa, Maria A; Sievers, Caroline et al

in International Journal of Cancer = Journal International du Cancer (2009), 125(9), 2122-6

Somatostatin analogs (SSA) with their potent antisecretory and antiproliferative effects are the main medical treatment option for patients with neuroendocrine tumors, such as gastroenteropancreatic and ... [more ▼]

Somatostatin analogs (SSA) with their potent antisecretory and antiproliferative effects are the main medical treatment option for patients with neuroendocrine tumors, such as gastroenteropancreatic and acromegaly-associated growth hormone secreting pituitary tumors. Although a good portion of acromegalic patients gets normalized after SSA treatment, strict hormonal control is not achieved in a sizeable proportion of these patients. The reasons for this incomplete response to SSA treatment are unclear. We have found that the tumor suppressor ZAC1 (LOT1/PLAGL1) is essential for the antiproliferative effect of SSA in pituitary tumor cells. The aim of the present retrospective cohort study was to determine whether ZAC1 immunoreactivity in archival somatotrophinoma tissue derived from 45 patients with acromegaly routinely pretreated with SSA before surgery, was associated with response to SSA (normalization of GH, IGF-I and presence of tumor shrinkage). All tumors displayed ZAC1 immunoreactivity [weak (+; n = 15), moderate (++; n = 16) and strong (+++; n = 14)]. A significant positive correlation was found between strong ZAC1 immunoreactivity and IGF-I normalization and presence of tumor shrinkage after SSA treatment, which was not affected by age at diagnosis, gender or duration of SSA treatment. These in vivo data combined with the antiproliferative properties of ZAC1/Zac1 provide evidence of a mechanistic role for this transcription factor on SSA induced tumor shrinkage and hormone normalization. [less ▲]

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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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