References of "Daly, Adrian"
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See detailAIP mutations and gigantism
Rostomyan, Liliya ULg; Potorac, Iulia ULg; BECKERS, Pablo ULg et al

in Annales d'Endocrinologie (2017)

AIP mutations are rare in sporadic acromegaly but they are seen at a higher frequency among certain specific populations of pituitary adenoma patients (pituitary gigantism cases, familial isolated ... [more ▼]

AIP mutations are rare in sporadic acromegaly but they are seen at a higher frequency among certain specific populations of pituitary adenoma patients (pituitary gigantism cases, familial isolated pituitary adenoma (FIPA) kindreds, and patients with macroadenomas who are diagnosed ≤ 30 years). AIP mutations are most prevalent in patients with pituitary gigantism (29% of this group were found to have mutations in AIP gene). These data support targeted genetic screening for AIP mutations/deletions in these groups of pituitary adenoma patients. Earlier diagnosis of AIP-related acromegaly-gigantism cases enables timely clinical evaluation and treatment, thereby improving outcomes in terms of excessive linear growth and acromegaly comorbidities. Bien que les mutations du gène AIP soient rares dans les cas d’acromégalie sporadique, l’importance de ces mutations est établie dans des populations spécifiques de patients telles que les patients qui souffrent de familial isolated pituitary adenomas (FIPA), de gigantisme ou qui présentent un macroadénome hypophysaire avant l’âge de 30 ans. C’est dans le gigantisme qu’elles sont le plus fréquemment retrouvées (29 % des géants présentent une mutation de ce gène). Dans ces populations, nos données suggèrent qu’il est utile de réaliser un screening ciblé pour les mutations ou délétions du gène AIP. La reconnaissance précoce des cas d’acromégalie et de gigantisme permet une évaluation clinique et un traitement appropriés de ces patients. Elle contribue à améliorer les résultats des traitements tant en terme de croissance excessive qu’en ce qui concerne les comorbidités liées à l’acromégalie. [less ▲]

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See detailAdipsic diabetes insipidus revealing a bifocal intracranial germinoma
KREUTZ, Julie ULg; Potorac, Iulia ULg; LUTTERI, Laurence ULg et al

in Annales d'Endocrinologie (2017)

Abstract Adipsic diabetes insipidus is a rare complication of intracranial tumors in which impaired antidiuretic hormone secretion is associated with the loss of thirst sensation. Here, we present the ... [more ▼]

Abstract Adipsic diabetes insipidus is a rare complication of intracranial tumors in which impaired antidiuretic hormone secretion is associated with the loss of thirst sensation. Here, we present the case of a patient with bifocal intracranial germinoma, diagnosed due to symptoms mainly caused by adipsic diabetes insipidus. This is, to our knowledge, the first case of adipsic diabetes insipidus revealing an intracranial germinoma reported in the literature. We describe the diagnostic procedures and the three-year follow-up of this patient. Management of intracranial germ-cell tumors is made complex by the wide range of histological features. Although germinomas have a generally better prognosis than most nongerminomatous tumors, they can have severe or even life-threatening presentations. Adipsic diabetes insipidus is one such severe presentation and its rarity can make it difficult to recognize and manage. Awareness of this potential entity is therefore important for clinical practice. Le diabète insipide adipsique est une des rares complications des tumeurs intracrâniennes. Il associe une baisse de la sécrétion d’hormone antidiurétique à une perte de la sensation de soif et ilsignale souvent la présence d’une lésion qui atteint ou envahit l’hypothalamus. Nous présentons le cas d’une patiente avec un germinome intracrânien bifocal diagnostiqué devant un tableau de diabète insipide adipsique. À notre connaissance, il s’agit du premier cas de la littérature d’un diabète insipide révélant un germinome intracrânien. La prise en charge des tumeurs germinales intracrâniennes est complexe du fait des phénotypes histologiques divers. Bien que les germinomes ont généralement un meilleur pronostic que les tumeurs non-germinomateuses, ils peuvent avoir des présentations sévères. Le diabète insipide adipsique est une de ces présentations sévères et sa rareté peut rendre son diagnostic et sa prise en charge difficiles. La reconnaissance de cette entité potentielle est, dès lors, importante pour la pratique clinique [less ▲]

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See detailX-LAG: How did they grow so tall?
BECKERS, Albert ULg; Rostomyan, Liliya ULg; Potorac, Iulia ULg et al

in Annales d'Endocrinologie (2017)

X-linked acrogigantism (XLAG) is a new, pediatric-onset genetic syndrome, due to Xq26.3 microduplications encompassing the GPR101 gene. XLAG has a remarkably distinct phenotype with disease onset ... [more ▼]

X-linked acrogigantism (XLAG) is a new, pediatric-onset genetic syndrome, due to Xq26.3 microduplications encompassing the GPR101 gene. XLAG has a remarkably distinct phenotype with disease onset occurring before the age of 5 in all cases described to date, which is significantly younger than in other forms of pituitary gigantism. These patients have mixed GH and prolactin positive adenomas and/or mixed-cell hyperplasia and highly elevated levels of GH/IGF-1 and prolactin. Given their particularly young age of onset, the significant GH hypersecretion can lead to a phenotype of severe gigantism with very advanced age-specific height Z-scores. If not adequately treated in childhood, this condition results in extreme final adult height. XLAG has a clinical course that is highly similar to some of the tallest people with gigantism in history. « X-linked acrogigantism » (XLAG) est un syndrome pédiatrique récemment décrit, lié à des microduplications du chromosome Xq26.3, englobant le gène GPR101, responsable de l’affection. Les patients XLAG présentent un phénotype remarquablement distinct des autres cas de gigantisme hypophysaire. Dans tous les cas décrits, la maladie s’exprime avant 5 ans soit beaucoup plus tôt que dans les autres formes. Les patients ont habituellement un gros adénome ou une hyperplasie mixte pour la GH et la prolactine et des taux très élevés de GH/IGF1 et prolactine. En raison de son début très précoce, l’hypersécrétion importante de GH peut conduire à un gigantisme extrêmement sévère avec un Z-score très important pour l’âge. Si cette condition n’est pas traitée pendant l’enfance, elle peut conduire à une taille finale extrême. XLAG montre une évolution clinique similaire à celle observée chez les géants les plus grands de l’histoire. [less ▲]

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See detailStable GPR101 over-Expressing Cell Lines As an Invaluable Tool for Functional Studies, Ligand Screening, and the Identification of Deregulated Genes/Pathways in Patients with X-Linked Acrogigantism
Trivellin, Giampaolo; Janjic, Maria; Larco, Darwin et al

Poster (2017, April 02)

Background: GPR101 is an orphan G protein-coupled receptor (GPCR) that is duplicated in patients with X-linked acrogigantism (X-LAG) and over-expressed in their GH- and PRL-secreting tumors. GPR101 is a ... [more ▼]

Background: GPR101 is an orphan G protein-coupled receptor (GPCR) that is duplicated in patients with X-linked acrogigantism (X-LAG) and over-expressed in their GH- and PRL-secreting tumors. GPR101 is a constitutively active GPCR that strongly activates the cAMP pathway. To elucidate the mechanisms through which GPR101 causes GH over-secretion we generated HEK293 and GH/PRL-secreting (GH3) cells with stable GPR101 expression. Methods: Both cell lines were created via direct integration of a human GPR101-coding sequence into their genome. In HEK293 cells this was achieved by transient transfection of a GPR101-expressing plasmid, while GH3 were transduced with GPR101 lentiviral particles. Cells were selected with appropriate antibiotics and the surviving clones expanded. GPR101 expression was quantified by RT-qPCR and immunofluorescence/western blotting. Cell proliferation (MTT assay), cAMP levels (125I-labeled cAMP tracer), and calcium signaling (FURA 2 AM) were determined. RNA was extracted from both cell lines and subjected to RNA-seq. Differential gene expression between control and GPR101-expressing cells and pathway analysis was carried out with the Stirplate and MetaCore softwares, respectively. De-regulated genes were validated by RT-qPCR. Results: High GPR101 expression was achieved in both cell lines and confirmed at the mRNA and protein level. GPR101-expressing cells proliferated at different rates from the respective controls: GPR101-HEK293 cells were slow-dividing, while GPR101-GH3 divided faster. cAMP production was enhanced in GPR101-GH3 and accompained by increased excitability of cells. Differential expression analysis in HEK293 cells revealed several up-regulated and few down-regulated genes. Among the genes with high expression, several were linked to the cAMP pathway: CGA, PCK1, LINC00473 and PDE3A. Enrichment analysis ranked cytoskeleton remodeling and cell cycle regulation (inhibition of G1/S transition) as the most relevant pathways. In GH3 cells most of the genes with a significantly different expression encoded for membrane-localized proteins, among which were ion channels (Trpm8, Kcnj1), GPCRs (Trhr), and calcium sensors (Syt4, Anxa1). Biological processes associated with these genes are: vesicle transport and fusion, cytoskeleton organization, and energy homeostasis. Conclusions: These results show that the intrinsic activity of GPR101 strongly stimulates cAMP production and this in turn facilitates voltage-gated calcium influx. Changes in cAMP/calcium signaling are accompanied with faster/slower cell division depending on the cell type. Accordingly, several genes associated with these and related pathways are differentially expressed. The establishment of these cell lines will be of paramount importance to validate putative GPR101 ligands and to conduct functional studies. [less ▲]

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See detailPrimary hypertrophic osteoarthropathy due to a novel SLCO2A1 mutation masquerading as acromegaly
Mangupli, Ruth; Daly, Adrian ULg; Cuauro, Elvia et al

in Endocrinology, Diabetes and Metabolism Case Reports (2017)

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See detailThe dual SSTR2/5 specific somatostatin analog, AP102, does not affect glucose metabolism in diabetic ZDF rats: a comparative 14-day infusion study versus pasireotide
Daly, Adrian ULg; Sumeray, Mark

in Abstract Book of the 15th International Pituitary Congress (2017, March 29)

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See detailGenetics of Pituitary Tumor Syndromes
Daly, Adrian ULg; BECKERS, Albert ULg

in Melmed, Shlomo (Ed.) The Pituitary (2017)

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See detailPaleogenetic study of ancient DNA suggestive of X-Linked acrogigantism
Beckers, Albert ULg; Fernandes, Daniel; Fina, Frederic et al

in Endocrine-Related Cancer (2017)

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See detailSomatic mosaicism is implicated in the etiology of XLAG syndrome
Rostomyan, Liliya ULg; Daly, Adrian ULg; Yuan, Bo et al

in Abstract book : Symposium "Perspectives in Endocrinology" (2017, January)

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See detailGenetic predisposition to breast cancer occuring in a male-to-female transsexual patient
Potorac, Iulia ULg; CORMAN, Vinciane ULg; Manto, Florence ULg et al

in Abstract book : Symposium "Perspectives in Endocrinology" (2017, January)

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See detailA multivariable prediction model for pegvisomant dosing: monotherapy and in combination with long-acting somatostatin analogues
Franck, Sanne Elisabeth; Korevaar, Tim; PETROSSIANS, Patrick ULg et al

in European Journal of Endocrinology (2017)

Background: Effective treatment of acromegaly with pegvisomant (PEGV), a growth hormone receptor antagonist, requires an appropriate dose titration. PEGV doses vary widely among individual patients, and ... [more ▼]

Background: Effective treatment of acromegaly with pegvisomant (PEGV), a growth hormone receptor antagonist, requires an appropriate dose titration. PEGV doses vary widely among individual patients, and various covariates may affect its dosing and pharmacokinetics. Objective: To identify predictors of the PEGV dose required to normalize insulin-like growth factor I (IGF-I) levels during PEGV monotherapy and in combination with long-acting somatostatin analogues (LA-SSAs). 188) were meta-analysed as a form of external replication to study the predictors of PEGV dosing in addition to LA-SSA, the LAS (n=83) was used to study the predictors of PEGV monotherapy dosing. Multivariable regression models were used to identify predictors of the PEGV dose required to normalize IGF-I levels. <0.001, p=<0.001, p=0.028 and p=0.047, respectively). Taken together, these characteristics predicted the PEGV normalization dose correctly in 63.3% of all patients within a range of +/- 60 mg/week (21.3% within a range of +/- 20 mg/week). For monotherapy, only weight was associated with the PEGV normalization dose (p=<0.001) and predicted this dosage correctly in 77.1% of all patients within a range of +/- 60 mg/week (31.3% within a range of +/- 20 mg/week). Conclusion: In this study, we show that IGF-I levels, weight, height and age can contribute to define the optimal PEGV dose in order to normalize IGF-I levels in addition to LA-SSA. For PEGV monotherapy, only the patient's weight was associated with the IGF-I normalization PEGV dosage. [less ▲]

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See detailTransdifferentiation of Neuroendocrine Cells: Gangliocytoma Associated With Two Pituitary Adenomas of Different Lineage in MEN1.
Sergeant, Camille; Jublanc, Christel; Leclercq, Delphine et al

in American Journal of Surgical Pathology (2017)

Gangliocytomas are rare and benign neuronal cell tumors, mostly found in the hypothalamic and sellar regions. Their histogenesis is still the subject of discussions. Herein we present a unique case of a ... [more ▼]

Gangliocytomas are rare and benign neuronal cell tumors, mostly found in the hypothalamic and sellar regions. Their histogenesis is still the subject of discussions. Herein we present a unique case of a pituitary gangliocytoma associated with a prolactinoma and a corticotroph adenoma in a patient affected by MEN1. The histologic study revealed shared features between adenomatous and neuronal cells, supporting the etiological hypothesis of a common origin or a phenomenon of transdifferentiation. Furthermore, gangliocytoma could be a new tumor related to MEN1. The clinical and histologic observations are discussed and the literature on the topic is reviewed. [less ▲]

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See detailThe role of AIP mutations in pituitary adenomas: 10 years on
Daly, Adrian ULg; BECKERS, Albert ULg

in Endocrine (2016)

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See detailProspective, long-term study of the effect of cabergoline on valvular status in patients with prolactinoma and idiopathic hyperprolactinemia.
VROONEN, Laurent ULg; Lancellotti, Patrizio ULg; Garcia, Monica Tome et al

in Endocrine (2016)

Since the 1990's cabergoline has been the treatment of choice in prolactinoma, as it permits rapid and effective hormonal and tumor control in most cases. Evidence of cardiac valvulopathy was demonstrated ... [more ▼]

Since the 1990's cabergoline has been the treatment of choice in prolactinoma, as it permits rapid and effective hormonal and tumor control in most cases. Evidence of cardiac valvulopathy was demonstrated in Parkinson's disease patients treated with dopamine agonists. Retrospective studies in prolactinoma patients treated with cabergoline at lower doses did not show such an effect. However, few prospective data with long-term follow-up are available. The aim of this study was to assess the safety of cabergoline regarding cardiac valvular status during prospective follow-up in patients treated for prolactinoma or idiopathic hyperprolactinemia. We report here a series of 100 patients (71F; median age at diagnosis: 41.5 years) treated with cabergoline for endocrine diseases (prolactinoma n = 89, idiopathic hyperprolactinemia n = 11). All patients underwent complete transthoracic echocardiographic studies at baseline and during long-term prospective surveillance using the same equipment and performed by the same technicians. The median interval between baseline and last follow-up echocardiographic studies while on cabergoline was 62.5 months (interquartile range: 34.75-77.0). The median total duration of cabergoline treatment was 124.5 months (interquartile range: 80.75-188.75) and the median cumulative total dose of cabergoline was 277.8 mg (interquartile range : 121.4-437.8 mg) at last follow-up. We found no clinically relevant alterations in cardiac valve function or valvular calcifications with cabergoline treatment. Our data suggest that findings from retrospective analyses are correct and that cabergoline is a safe chronic treatment at the doses used typically in endocrinology. [less ▲]

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See detailSomatic mosaicism is implicated in the etiology of XLAG syndrome
Rostomyan, Liliya ULg; Daly, Adrian ULg; Yuan, Bo et al

in 26nd meeting of the Belgian Endocrine Society - Abstract book (2016, October)

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See detailHypogonadism due to a novel inactivating mutation of the luteinizing hormone beta subunit (LHB) gene leading to impaired protein trafficking
Potorac, Iulia ULg; Rivero-muller, a; Trehan, A et al

in 26nd meeting of the Belgian Endocrine Society - Abstract book (2016, October)

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See detailT2-weighted MRI signal predicts hormone and tumor responses to somatostatin analogs in acromegaly.
Potorac, Iulia ULg; PETROSSIANS, Patrick ULg; Daly, Adrian ULg et al

in Endocrine-Related Cancer (2016), 23(11), 871881

GH-secreting pituitary adenomas can be hypo-, iso- or hyperintense on T2-weighted MRI sequences. We conducted the current multicenter study in a large population of patients with acromegaly to analyze the ... [more ▼]

GH-secreting pituitary adenomas can be hypo-, iso- or hyperintense on T2-weighted MRI sequences. We conducted the current multicenter study in a large population of patients with acromegaly to analyze the relationship between T2-weighted signal intensity on diagnostic MRI and hormonal and tumoral responses to somatostatin analogs (SSA) as primary monotherapy. Acromegaly patients receiving primary SSA for at least 3 months were included in the study. Hormonal, clinical and general MRI assessments were performed and assessed centrally. We included 120 patients with acromegaly. At diagnosis, 84, 17 and 19 tumors were T2-hypo-, iso- and hyperintense, respectively. SSA treatment duration, cumulative and mean monthly doses were similar in the three groups. Patients with T2-hypointense adenoma had median SSA-induced decreases in GH and IGF-1 of 88% and 59% respectively, which were significantly greater than the decreases observed in the T2-iso- and hyperintense groups (p<0.001). Tumor shrinkage on SSA was also significantly greater in the T2-hypointense group (38%) compared with the T2-iso- and hyperintense groups (8% and 3%, respectively; p<0.0001). The response to SSA correlated with the calculated T2-intensity: the lower the T2-weighted intensity, the greater the decrease of random GH (p<0.0001, r=0.22), IGF-1 (p<0.0001, r=0.14) and adenoma volume (p<0.0001, r=0.33). The T2-weighted signal intensity of GH-secreting adenomas at diagnosis correlates with the hormone reduction and tumor shrinkage in response to primary SSA treatment in acromegaly. This study supports its use as a generally available predictive tool at diagnosis that could help to guide subsequent treatment choices in acromegaly. [less ▲]

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See detailCharacterization of GPR101 transcripts structure and expression patterns
Trivellin, Giampaolo; Ivana, Bjelobaba; Daly, Adrian ULg et al

in Journal of Molecular Endocrinology (2016)

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