References of "Beckers, Albert"
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See detailLe phénotype d’Akhenaton ; revue critique entre canons artistiques et expression pathologique.
JEDIDI, Zayd ULiege; JEDIDI, Haroun ULiege; LAVEAUX, Elisabeth ULiege et al

in Revue Médicale de Liège (in press)

Of all the royal families of ancient or modern fame, few are as iconic as the eighteenth dynasty of pharaohs of the New Kingdom of Egypt, whose opulence and deeds we are still familiar to nearly 3,500 ... [more ▼]

Of all the royal families of ancient or modern fame, few are as iconic as the eighteenth dynasty of pharaohs of the New Kingdom of Egypt, whose opulence and deeds we are still familiar to nearly 3,500 years after their time. Tenth pharaoh of this dynasty and father of Tutankhamun, Akhenaten (Amenhotep/Amenhotep IV) still fascinates Egyptologists and history lovers through the many questions surrounding his atypical rule. One of the most striking aspects of the so-called Amarna period concerns the representations of the pharaoh himself, very confusing compared to the traditional iconography of the New Kingdom. These intriguing portraits of Pharaoh raised a whole lot of medical assumptions, more or less substantiated. We review here the main theories developed throughout history. [less ▲]

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See detailAdvances in diagnosis and management of familial pituitary adenomas
JEDIDI, Haroun ULiege; ROSTOMYAN, Lilith; POTORAC, Iulia et al

in International Journal of Endocrine Oncology (in press)

Familial pituitary adenomas accounts for approximately 5-8 % of all pituitary adenomas. Besides the adenomas occurring as part of syndromic entities that bring together several endocrine or other systems ... [more ▼]

Familial pituitary adenomas accounts for approximately 5-8 % of all pituitary adenomas. Besides the adenomas occurring as part of syndromic entities that bring together several endocrine or other systems disorders, 2-3% of the familial pituitary adenomas fit into the familial isolated pituitary adenomas (FIPA) syndrome. 20% of FIPA syndromes have shown mutations in the AIP gene and have distinct clinical characteristics. Recent findings have isolated a new non-AIP FIPA syndrome called X-LAG, resulting from duplication in GPR-101 gene. These new advances in the field of pituitary disease are opening up a new challenging domain to both clinician and researcher. This review will focus on these last findings and their contribution to the diagnosis and the management of familial pituitary adenomas. [less ▲]

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See detailEpidemiology of Prolactinomas
Beckers, Albert ULiege

Scientific conference (2017, September 07)

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See detailAcromegaly at diagnosis in 3173 patients from the Liege Acromegaly Survey (LAS) database.
PETROSSIANS, Patrick ULiege; Daly, Adrian ULiege; Natchev, Emil et al

in Endocrine-Related Cancer (2017)

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 ... [more ▼]

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; p<0.001). The median delay from first symptoms to diagnosis was two years longer in females (p=0.015). Ages at diagnosis and first symptoms increased significantly over time (p<0.001). Tumors were larger in males than females (p<0.001); tumor size and invasion were inversely related to patient age (p<0.001). Random GH at diagnosis correlated with nadir GH levels during OGTT (p<0.001). GH was inversely related to age in both sexes (p<0.001). Diabetes mellitus was present in 27.5%, hypertension in 28.8%, sleep apnea syndrome in 25.5% and cardiac hypertrophy in 15.5%. Serious cardiovascular outcomes like stroke, heart failure and myocardial infarction were present in <5% at diagnosis. Erythrocyte levels were increased and correlated with IGF-1 values. Thyroid nodules were frequent (34.0%); 820 patients had colonoscopy at diagnosis and 13% had polyps. Osteoporosis was present at diagnosis in 12.3% and 0.6-4.4% had experienced a fracture. This study of >3100 patients is the largest international acromegaly database and shows clinically relevant trends in the characteristics of acromegaly at diagnosis. [less ▲]

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See detailLuteinizing Hormone Deficiency: Historical Views and Perspectives
VALDES SOCIN, Hernan Gonzalo ULiege; Daly, Adrian ULiege; BECKERS, Albert ULiege

in Austin Andrology (2017), 2(1), 1-2

Fertility in men requires normal testicular development, which is controlled by chorionic gonadotropin (hCG) in utero and thereafter by luteinizing hormone (LH) and follicle-stimulating hormone (FSH ... [more ▼]

Fertility in men requires normal testicular development, which is controlled by chorionic gonadotropin (hCG) in utero and thereafter by luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Some rare observations, such as, mutations in the luteinizing hormone subunit beta gene [2] have contributed substantially to our understanding of reproductive development and male infertility. In this editorial we summaryze current knowledge about beta LH mutations and polymorphism in men and discuss fertility issues. [less ▲]

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See detailX-LAG ou comment ils sont devenus si grands ?
BECKERS, Albert ULiege

Scientific conference (2017, June 09)

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See detailDu plus petit au plus grand
Beckers, Albert ULiege

Scientific conference (2017, June 08)

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See detailControverse : Prétraitement par analogues de la somatostatine avant chirurgie de l'acromégalie
Beckers, Albert ULiege

Scientific conference (2017, May 12)

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See detailUne mosaïque de géants
Beckers, Albert ULiege

Scientific conference (2017, May 11)

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See detailFrom the shortest to the tallest
Beckers, Albert ULiege

in Annales d'Endocrinologie (2017), 78

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See detailAIP mutations and gigantism
Rostomyan, Liliya ULiege; Potorac, Iulia ULiege; BECKERS, Pablo ULiege 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 ULiege; Potorac, Iulia ULiege; LUTTERI, Laurence ULiege 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 detailGPR101 orphan GPCR: a novel cause of growth hormone deregulation
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine ULiege et al

Poster (2017, May)

GPR101 is an orphan G-protein coupled receptor with unknown ligand. In 2014, an international study clearly pointed to a strong association between this receptor and the X-linked acrogigantism (X-LAG ... [more ▼]

GPR101 is an orphan G-protein coupled receptor with unknown ligand. In 2014, an international study clearly pointed to a strong association between this receptor and the X-linked acrogigantism (X-LAG) syndrome, which begins in childhood and causes the “tallest giants”. The children (carriers of the GPR101 duplication on the X chromosome) grow abnormally even before they are one year old, secrete phenomenal quantities of growth hormone, and develop pituitary adenomas that do not respond to current therapies. The mechanism by which GPR101 contributes to increased growth hormone secretion is currently not known. Nevertheless, the lack of mechanistic insight into the function of GPR101 precludes its validation as a drug target. This lack of knowledge on GPR101 is the consequence of the paucity of specific pharmacological/research tools currently available. Therefore, we propose to study GPR101 functions and its role in growth hormone regulation. First, we determined the receptor cellular localization. We also deciphered its constitutive signalling pathways by detecting high cAMP levels. We completed our study with an examination of receptor coupling to other pathways and G proteins. Furthermore, we applied targeted mutagenesis to modulate the receptor constitutive activity in order to understand the receptor function at a molecular level. These GPR101 mutants will help us to understand the role of this receptor in GH regulation and/or to treat people suffering from pituitary dysfunction. This information is an absolute prerequisite to link molecular pharmacology of GPR101 with physiological functions. [less ▲]

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See detailX-linked acrogigantism syndrome
Beckers, Albert ULiege

Scientific conference (2017, May)

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See detailLa déficience en hormone lutéinisante: ses conséquences sur la reproduction
VALDES SOCIN, Hernan Gonzalo ULiege; potorac, iulia; LIBIOULLE, Cécile ULiege et al

in Urologic (2017), 13(1), 18-23

En physiologie de la reproduction, il est bien établi que les hormones glycoprotéiques hypophysaires LH (hormone lutéinisante) et FSH régulent de concert la production de stéroïdes sexuels (indispensables ... [more ▼]

En physiologie de la reproduction, il est bien établi que les hormones glycoprotéiques hypophysaires LH (hormone lutéinisante) et FSH régulent de concert la production de stéroïdes sexuels (indispensables à la virilisation et à la féminisation) ainsi que la gamétogenèse (spermatogenèse chez l’homme et folliculogenèse chez la femme). La sécrétion des gonadotrophines hypophysaires est à son tour stimulée par quelque 1.500 neurones hypothalamiques à GnRH (gonadotrophin releasing hormone) et inhibée par la GnIH (gonadotrophin nhibitory hormone), récemment identifiée (1). En amont de la GnRH, un ensemble de neuropeptides hypothalamiques tels que les kisspeptines, la neuroquinine B, la dinorphine, la leptine, etc., modulent sa sécrétion (Figure 1). Ces neuropeptides intègrent les différents signaux internes et de l’environnement, nécessaires à la puberté et, par la suite, à la reproduction. En corollaire de ces données physiologiques, les patients porteurs de mutations invalidant les gènes de la GnRH, des neuropeptides décrits et de leurs récepteurs souffrent d’un hypogonadisme hypogonadotrope. Ces patients présentent un déficit plus ou moins sévère de la sécrétion combinée de LH et de FSH (2, 3). Il a fallu attendre des observations rares, telles que des mutations de la sous-unité beta (β) de l’hormone lutéinisante, pour comprendre la contribution spécifique et isolée de cette hormone à la reproduction. Dans cet article, nous synthétisons les données historiques et récentes sur la déficience en hormone lutéinisante et ses conséquences sur la reproduction. [less ▲]

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See detailX-LAG: How did they grow so tall?
BECKERS, Albert ULiege; Rostomyan, Liliya ULiege; Potorac, Iulia ULiege 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 detailComment on “Hypogonadotrophic hypogonadism due to a mutation in the luteinizing hormone β-subunit gene”
VALDES SOCIN, Hernan Gonzalo ULiege; Daly, Adrian ULiege; BECKERS, Albert ULiege

in Korean Journal of Internal Medicine (The) (2017), 32(3), 566-567

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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 ULiege; Cuauro, Elvia et al

in Endocrinology, Diabetes and Metabolism Case Reports (2017)

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See detailHow the became the tallest of the world
Beckers, Albert ULiege

Scientific conference (2017, March 09)

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