References of "Daly, Adrian"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailAIP and MEN1 mutations and AIP immunohistochemistry in pituitary adenomas in a tertiary referral center.
Daly, Adrian ULiege; Cano, David A.; Venegas, Eva et al

in Endocrine Connections (2019)

BACKGROUND: Pituitary adenomas have a high disease burden due to tumor growth/invasion and disordered hormonal secretion. Germline mutations in genes such as MEN1 and AIP are associated with early onset ... [more ▼]

BACKGROUND: Pituitary adenomas have a high disease burden due to tumor growth/invasion and disordered hormonal secretion. Germline mutations in genes such as MEN1 and AIP are associated with early onset of aggressive pituitary adenomas that can be resistant to medical therapy. AIMS: We performed a retrospective screening study using published risk criteria to assess the frequency of AIP and MEN1 mutations in pituitary adenoma patients in a tertiary-referral center. METHODS: Pituitary adenoma patients with pediatric/adolescent onset, macroadenomas occurring </=30 years of age, familial isolated pituitary adenoma (FIPA) kindreds, and acromegaly or prolactinoma cases that were uncontrolled by medical therapy were studied genetically. We also assessed whether immunohistochemical staining for AIP (AIP-IHC) in somatotropinomas was associated with somatostatin analogs (SSA) response. RESULTS: Fifty-five patients met the study criteria and underwent genetic screening for AIP/MEN1 mutations. No mutations were identified and large deletions/duplications were ruled out using MLPA. In a cohort of sporadic somatotropinomas, low AIP-IHC tumors were significantly larger (p=0.002) and were more frequently sparsely-granulated (p=0.046) than high AIP-IHC tumors. No significant relationship between AIP-IHC and SSA responses was seen. CONCLUSIONS: Germline mutations in AIP/MEN1 in pituitary adenoma patients are rare and the use of published risk criteria did not identify cases in a large tertiary-referral setting. In acromegaly, low AIP-IHC was related to larger tumor size and more frequent sparsely-granulated subtype but no relationship with SSA-responsiveness was seen. The genetics of aggressive, treatment-resistant and familial pituitary adenomas remain largely unexplained and screening criteria could be significantly refined. [less ▲]

Detailed reference viewed: 20 (3 ULiège)
Full Text
Peer Reviewed
See detailEpidemiology and Management Challenges in Prolactinomas.
VROONEN, Laurent ULiege; Daly, Adrian ULiege; Beckers, Albert ULiege

in Neuroendocrinology (2019)

Clinically relevant pituitary adenomas are present in about 1 per 1000 of the general population and prolactinomas are by far the most common clinical subtype of pituitary adenomas. Usually prolactinomas ... [more ▼]

Clinically relevant pituitary adenomas are present in about 1 per 1000 of the general population and prolactinomas are by far the most common clinical subtype of pituitary adenomas. Usually prolactinomas affect pre-menopausal women and present with typical symptoms of menstrual disturbance and/or galactorrhea. They are generally managed with dopamine agonists to restore fertility and to control symptoms and tumour size. In a subset of prolactinomas, however, management remains challenging. Studies in recent years have identified the factors related to dopamine agonist resistance, such as, male sex, genetic features, and aggressive tumor behaviour. Certain other patient groups represent particular challenges for management, such as pediatric patients and pregnant women. Treatment with dopamine agonists is usually safe and effective, and adverse effects such as clinically relevant cardiac valvular complications and impulse control disorders may occur in isolated instances. A number of important disease characteristics of prolactinomas remain to be explained, such as the difference in sex prevalence before and after menopause, the higher prevalence of macroadenomas in older males and the biochemical mechanisms of resistance to dopaminergic agonists. [less ▲]

Detailed reference viewed: 26 (6 ULiège)
Full Text
Peer Reviewed
See detailGenetic Testing in Pituitary Adenomas: What, How, and In Whom?
Daly, Adrian ULiege; Beckers, Albert ULiege

in Endocrinología, Diabetes y Nutrición (2019), 66(2), 71-73

Detailed reference viewed: 35 (7 ULiège)
Full Text
Peer Reviewed
See detailThe causes and consequences of pituitary gigantism
Beckers, Albert ULiege; PETROSSIANS, Patrick ULiege; Hanson, Julien ULiege et al

in Nature Reviews. Endocrinology (2018), 14

In the general population, height is determined by a complex interplay between genetic and environmental factors. Pituitary gigantism is a rare but very important subgroup of patients with excessive ... [more ▼]

In the general population, height is determined by a complex interplay between genetic and environmental factors. Pituitary gigantism is a rare but very important subgroup of patients with excessive height, as it has an identifiable and clinically treatable cause. The disease is caused by chronic growth hormone and insulin-like growth factor 1 secretion from a pituitary somatotrope adenoma that forms before the closure of the epiphyses. If not controlled effectively, this hormonal hypersecretion could lead to extremely elevated final adult height. The past 10 years have seen marked advances in the understanding of pituitary gigantism, including the identification of genetic causes in \~50\% of cases, such as mutations in the AIP gene or chromosome Xq26.3 duplications in X-linked acrogigantism syndrome. Pituitary gigantism has a male preponderance, and patients usually have large pituitary adenomas. The large tumour size, together with the young age of patients and frequent resistance to medical therapy, makes the management of pituitary gigantism complex. Early diagnosis and rapid referral for effective therapy appear to improve outcomes in patients with pituitary gigantism; therefore, a high level of clinical suspicion and efficient use of diagnostic resources is key to controlling overgrowth and preventing patients from reaching very elevated final adult heights. [less ▲]

Detailed reference viewed: 44 (17 ULiège)
Full Text
See detailCardiovascular complications in pituitary gigantism (results of an international study)
ROSTOMYAN, Liliya ULiege; Daly, Adrian ULiege; Shah, N et al

in Abstract book : 18th Congress of the European Neuroendocrine Association - ENEA (2018, October 18)

Detailed reference viewed: 15 (6 ULiège)
Full Text
See detailCardiovascular complications in pituitary gigantism (results of an international study)
ROSTOMYAN, Liliya ULiege; Daly, Adrian ULiege; Shah et al

in Abstract book : 18th Congress of the European Neuroendocrine Association - ENEA (2018, October)

Detailed reference viewed: 32 (7 ULiège)
Full Text
See detailCardiovascular complications in pituitary gigantism (results of an international study)
ROSTOMYAN, Liliya ULiege; Daly, Adrian ULiege; Shah, N et al

in Abstract book - 28th meeting of the Belgian Endocrine Society (2018, October)

Detailed reference viewed: 32 (15 ULiège)
See detailGPR101 orphan receptor: a novel cause of growth hormone deregulation
Abboud, Dayana ULiege; Daly, Adrian ULiege; Laschet, Céline ULiege et al

Conference (2018, July 05)

Detailed reference viewed: 30 (6 ULiège)
Full Text
Peer Reviewed
See detailResistant Paediatric Somatotropinomas due to AIP Mutations: Role of Pegvisomant
Joshi, Kriti; Daly, Adrian ULiege; BECKERS, Albert ULiege et al

in Hormone Research in Paediatrics (2018)

Detailed reference viewed: 61 (12 ULiège)
Full Text
Peer Reviewed
See detailPheochromocytomas and pituitary adenomas in three patients with MAX exon deletions
Daly, Adrian ULiege; CASTERMANS, Emilie ULiege; Oudijk, Lindsey et al

in Endocrine-Related Cancer (2018), 25(5), 3742

Copy number variations (CNV), an important genetic mechanism in inherited tumor genetics, can affect large genetic regions or can be limited to smaller regions within genes, such deletions of single exons ... [more ▼]

Copy number variations (CNV), an important genetic mechanism in inherited tumor genetics, can affect large genetic regions or can be limited to smaller regions within genes, such deletions of single exons. Such exon deletions can be challenging to identify and sequencing can be normal in these cases. Multiplex ligation dependent probe amplification (MLPA) can identify CNV of individual exons. Mutations in the MAX gene are associated with a risk of sporadic and hereditary pheochromocytoma. As mutations in other pheochromocytoma related genes can also cause pituitary tumors (3P-Association), we studied whether MAX exon deletions were involved in the etiology of patients with an unexplained association of multiple endocrine neoplasia including pituitary adenoma and pheochromocytoma. Using MLPA we identified three patients with pheochromocytoma and pituitary adenomas who had normal MAX sequencing but presented germline heterozygous MAX exon deletions. The three patients had either acromegaly (n=2) or prolactinoma (n=1) in association with bilateral or recurrent pheochromocytoma. Two had germline heterozygous deletions of single exons of MAX, the other had a germline heterozygous deletion of MAX exons 1-3. MAX immunohistochemical staining was lost in the pheochromocytomas of all three patients and genetic analysis confirmed loss of heterozygosity in tumor DNA. A MAX exon deletion was also transmitted from one patient to a currently asymptomatic offspring. Screening studies of pheochromocytoma patients should take into account the potential for co-existing pituitary tumors. MLPA or other techniques to identify discrete MAX exon deletions should be considered in individuals with pheochromocytoma that are negative following comprehensive sequencing. [less ▲]

Detailed reference viewed: 89 (16 ULiège)
Full Text
Peer Reviewed
See detailCellular effects of AP102, a somatostatin analog with balanced affinities for the hSSTR2 and hSSTR5 receptors
Streuli, Jeremy; Harris, Alan G.; Cottiny, Cecilia et al

in Neuropeptides (2018), 68

Background Somatostatin analogs (SSAs) are first-line medical therapy for the treatment of acromegaly and neuroendocrine tumors that express somatostatin receptors (SSTR). Somatostatin suppresses ... [more ▼]

Background Somatostatin analogs (SSAs) are first-line medical therapy for the treatment of acromegaly and neuroendocrine tumors that express somatostatin receptors (SSTR). Somatostatin suppresses secretion of a large number of hormones through the stimulation of the five SSTR. However, unbalanced inhibition of secretion as observed with the highly potent SSAs pasireotide causes hyperglycaemia mainly by inhibiting insulin secretion. In contrast, AP102 a new SSAs has neutral effect on blood glucose while suppressing GH secretion. Our objective was to establish the cellular effects of AP102 on SSTR2 and SSTR5 that may explain the differences observed between AP102 and other SSAs. Methods We compared the binding and agonist activity of AP102 with somatostatin-14, octreotide and pasireotide in HEK293 cells transfected with human SSTR2 and SSTR5 receptors. SSAs signal transduction effects (cAMP concentrations) were measured in forskolin-treated cells in the presence of SSAs. Proliferation and apoptotic effects were determined and binding assays were performed using 125I- somatostatin-14. Results AP102 has comparable affinity and agonist effect to octreotide at SSTR2 (IC50's of 112 pM and 244 pM, respectively; EC50's of 230 pM and 210 pM, respectively) in contrast to pasireotide that exhibits a 12–27 fold higher IC50 (3110 pM) and about 5-fold higher EC50 (1097 pM). At SSTR5, AP102 has much higher affinity and stimulating effect than octreotide (IC50's of 773 pM and 16,737 pM, respectively; EC50's of 8526 pM and 26,800 pM), and an intermediate affinity and agonist effect between octreotide and pasireotide. AP102, octreotide and pasireotide have variable anti-proliferative effects on HEK cells transfected with SSTR2 and SSTR5. Conclusion AP102 is a new SSA that better reduces signaling at SSTR2 than SSTR5 and prevents cell proliferation at both receptors. The euglycaemic effect of AP102 observed in preclinical studies may be related to this intermediate agonistic potency between pasireotide and octreotide at SSTR2 and SSTR5. [less ▲]

Detailed reference viewed: 18 (4 ULiège)
Full Text
Peer Reviewed
See detailPituitary Tumors Associated With Multiple Endocrine Neoplasia Syndromes
Rostomyan, Liliya ULiege; Daly, Adrian ULiege; BECKERS, Albert ULiege

in Huhtamiemi, Ilpo (Ed.) Encyclopedia of Endocrine Diseases (2018)

Detailed reference viewed: 45 (14 ULiège)
Full Text
Peer Reviewed
See detailParaneoplastic secretion in parathyroid carcinoma: serum hCG as a tumor marker
VALDES SOCIN, Hernan Gonzalo ULiege; BETEA, Daniela ULiege; Daly, Adrian ULiege et al

in Acta Clinica Belgica (2017), 72(2), 5

Introduction Parathyroid carcinoma (PCa) is a rare presentation of primary hyperparathyroidism (PHPT), accounting for less than 1 % of cases. Differentiating parathyroid cancer from adenoma is clinically ... [more ▼]

Introduction Parathyroid carcinoma (PCa) is a rare presentation of primary hyperparathyroidism (PHPT), accounting for less than 1 % of cases. Differentiating parathyroid cancer from adenoma is clinically challenging. Rubin et al (2008) et al. suggested that urinary hCG might be a marker of disease progression in PCa. In this study, we aimed to investigate whether the hCG+β kit from Roche Diagnostics could distinguish PCa patients from PHPT. Material and methods We studied a series of 8 patients suffering from advanced PCa, referred to the CHU de Liege. A control group of 20 PHPT patients was used as comparative. hCG+β kit on Cobas (Roche Diagnostics) uses 2 monoclonal antibodies that recognize holo-hCG, nicked hCG, β-core fragment and free β-subunit. Limits of hCG detection and quantification are <0.1 and <0.6 mUI/mL. In non pregnant and postmenopausal women and in men, hCG (p95) is <1 (5.3), <7 mUI/mL (8.3) and <2 (2.6) mUI/mL, respectively. Results. The 8 PCa patients (3 women) presented high serum hCG values at: 1.29, 3.46, 5.7, 24.2, 31.2, 34.1, 36.5 and 164 mUI/mL. Values of 1.29 and 3.46 were obtained in 2 postmenopausal women. The lowest value was presented by the only still alive patient. There was a significant correlation (r=0.786; ρ <0.05) between hCG and PTH and a borderline correlation (r=0.750; ρ =0.05) between hCG and calcium concentrations. All PHP patients presented undetectable hCG values. Conclusions These results suggest that serum hCG might have the potential to discriminate between parathyroid adenomas and carcinomas, with a sensibility of 75% (6/8) and a specificity of 100% (0/20). The only patient still alive presented the lowest hCG values. If hCG could be predictive of PCa survival needs to be studied in a larger series of patients. [less ▲]

Detailed reference viewed: 40 (4 ULiège)
Full Text
See detailLong-term management of resistant acromegaly with pasireotide LAR in 2 cases with a familial AIP Mutation
Rostomyan, Liliya ULiege; Daly, Adrian ULiege; Pellegata, N et al

in Acta Clinica Belgica (2017, October 07)

Detailed reference viewed: 28 (6 ULiège)