Searchable abstracts of presentations at key conferences in endocrinology

ea0037ep808 | Pituitary: clinical | ECE2015

Trial design of phase IIIb, open-label, single arm study to evaluate efficacy and safety of pasireotide LAR in patients with inadequately-controlled acromegaly despite treatment with first-generation somatostatin analogues

Gadelha Monica R , Pedroncelli Alberto M , Kandra Albert , Resendiz Karina Hermosillo , Colao Anna Maria

Introduction: The present study is designed to evaluate the efficacy and safety of pasireotide-long-acting release (LAR) in patients with acromegaly inadequately controlled after ≧3 mo treatment with the maximal approved doses of first-generation SSAs.Methods: Phase IIIb, multicentre, single-arm, open-label study.Patients: Adults (N~112) with inadequately controlled acromegaly (mean GH>1 μg/l and IGF-1>1.3xULN) desp...

ea0037gp.19.09 | Pituitary–Acromegaly | ECE2015

Management of pasireotide-induced hyperglycaemia with proactive monitoring and early intervention: key learnings from the phase III, 24-week PAOLA study

Gadelha Monica R , Brue Thierry , Fleseriu Maria , Shimon Ilan , Resendiz Karina Hermosillo , Kandra Albert , Pedroncelli Alberto M , Colao AnnaMaria

Introduction: In PAOLA study, pasireotide showed superior efficacy over continued treatment with octreotide/lanreotide in patients with inadequately-controlled acromegaly; 64% of patients receiving pasireotide long-acting release (LAR) reported hyperglycaemia-related adverse events. Pasireotide has been shown to inhibit insulin secretion. The aim of this exploratory analysis was to investigate the effect of timing of antidiabetic medication (ADM) intervention on the fasting pl...

ea0037ep800 | Pituitary: clinical | ECE2015

Metformin-based oral antidiabetic therapy proved effective in hyperglycaemia associated with pasireotide in patients with acromegaly

Colao Anna Maria , Gu Feng , Gadelha Monica R , Lely Aart J van der , Fleseriu Maria , Passos Vanessa , Ravichandran Shoba , Chen Yin Miao , Bronstein Marcello D

Introduction: High affinity binding of pasireotide for both sst2 and sst5 leads to its enhanced efficacy in treatment of acromegaly but results in decreased secretion of insulin, incretins (GLP-1 and GIP) and, to a lesser extent, glucagon. Metformin may be a good option in patients with acromegaly experiencing hyperglycaemia with pasireotide as it improves GLP-1 secretion. We analysed data from a 12-month, Phase III, randomised study in medically naï...

ea0081oc4.6 | Oral Communications 4: Pituitary and Neuroendocrinology 1 | ECE2022

ACROBAT advance: once daily, oral paltusotine treatment maintained long-term igf-1 at levels previously achieved with injectable long-acting somatostatin receptor ligands (LA-SRLs)

Gadelha Monica R , Randeva Harpal , Gordon Murray B , Mezosi Emese , Doknic Mirjana , Toth Miklos , Boguszewski Cesar L , Nichols Melissa , Jochelson Theresa , Henley Scott , Patel Meenal , Mendez Debbie Koh , Ferrara-Cook Christine , Krasner Alan , Casagrande Alessandra , Struthers R Scott

Paltusotine is a once-daily, oral, nonpeptide somatostatin receptor type 2 (SST2) specific agonist, in development for the treatment of acromegaly and neuroendocrine tumors. We report interim results from ACROBAT Advance (NCT04261712), an ongoing, multicenter, open-label, long-term extension study of paltusotine in subjects with acromegaly who previously completed either Phase 2 study ACROBAT Edge (NCT03789656) or Evolve (NCT03792555). ACROBAT Edge enrolled 47 subjects with el...

ea0067o34 | Oral Presentations | EYES2019

Splicing machinery is dysregulated in pituitary neuroendocrine tumors (PitNETs) and associated with aggressiveness features

Jimenez-Vacas Juan M , Vazquez-Borrego Mari C , Fuentes-Fayos Antonio C , Venegas-Moreno Eva , Gadelha Monica R , Galvez-Moreno Maria A , Soto-Moreno Alfonso , Gahete Manuel D , Castano Justo P , Luque Raul M

Objective and methods: Recent studies suggest that altered alternative splicing and, consequently, appearance of an abnormal splicing pattern and even of aberrant/oncogenic splicing-variants, represent a common molecular feature of most tumor pathologies, including Pituitary Neuroendocrine Tumors (PitNETs). However, the putative alteration, pathophysiological role and potential therapeutic utility of splicing machinery components [i.e. spliceosome-components (SCs) and splicing...

ea0044p167 | Neuroendocrinology and pituitary | SFEBES2016

Polymorphism or mutation? – The role of the R304Q missense AIP mutation in the predisposition to pituitary adenoma

Mothojakan Nadira B , Ferrau Francesco , Dang Mary N , Barlier Anne , Chanson Philippe , Occhi Gianluca , Daly Adrian F , Schofl Christof , Dal Jakob , Gadelha Monica R , Ludman Mark , Kapur Sonal , Iacovazzo Donato , Korbonits Marta

Introduction: Heterozygous mutations in the AIP gene are associated with young-onset pituitary adenomas while homozygous loss of AIP in animal models is lethal. As early diagnosis could lead to better outcomes, family members of AIP mutation-positive patients need follow up. The R304Q variant is commonly described as pathogenic based on clinical assessment. However, it is also present in the general population (minor-allele-frequency (MAF) 0.0007&#15...

ea0037ep810 | Pituitary: clinical | ECE2015

Pasireotide long-acting release maintains biochemical control in patients with acromegaly: results from the extension of randomised, Phase III, PAOLA study

Colao Anna Maria , Bronstein Marcello D , Brue Thierry , Coculescu Mihail , Marinis Laura De , Fleseriu Maria , Guitelman Mirtha A , Pronin Vyacheslav , Raverot Gerald , Shimon Ilan , Fleck Juergen , Kandra Albert , Pedroncelli Alberto M , Gadelha Monica R

Introduction: The PAOLA study in patients with inadequately-controlled acromegaly (n=198) demonstrated superior efficacy of pasireotide long-acting release (LAR; 40 mg/60 mg) in biochemical control (GH <2.5 μg/l and normalized IGF-1) vs continued treatment with octreotide LAR 30 mg/lanreotide Autogel 120 mg (15.4% and 20.0% vs 0%). Here we report preliminary data from the extension phase of PAOLA at wk28.Methods: Pasireotide-LAR (40 mg/...

ea0063oc5.3 | Adrenal 1 | ECE2019

SF3B1 as novel target for the treatment of multiple endocrine-related cancers

Jimenez-Vacas Juan M , Lopez-Canovas Juan L , Vazquez-Borrego Mari C , Pedraza-Arevalo Sergio , del Rio-Moreno Mercedes , Herrero-Aguayo Vicente , Saez-Martinez Prudencio , Montero-Hidalgo Antonio J , Encinas Ricardo Blazquez , Lara-Lopez Araceli , Perez-Gomez Jesus M , Gomez-Gomez Enrique , Herrera-Martinez Aura , Gadelha Monica R , Castano Justo P , Gahete Manuel D , Luque Raul M

The intrinsic heterogeneity of endocrine-related cancers (ERCs) hampers the identification and development of global and effective therapeutic treatments for these pathologies. However, the dysregulation of the splicing process has been postulated as a new common hallmark shared by most cancer types, since it is associated with the appearance of splicing variants with oncogenic potential (e.g. CD44v6, BCL-Xs, AR-v7, SST5TMD4, In1-ghrelin...

ea0049gp160 | Neuroendocrinology &amp; Growth Hormones | ECE2017

Somatic mutations in USP8 are frequent events in pituitary tumors causing Nelson’s syndrome

Perez-Rivas Luis G , Theodoropoulou Marily , Puar Troy H , Fazel Julia , Stieg Mareike R , Ferrau Francesco , Assie Guillaume , Gadelha Monica R , Deutschbein Timo , Fragoso Maria C , Kusters Benno , Korbonits Marta , Bertherat Jerome , Stalla Gunter K , Hermus Ad R , Beuschlein Felix , Reincke Martin

Recent studies have reported a high prevalence of USP8 mutations in corticotroph adenomas causing Cushing’s disease. Nelson’s syndrome is a potentially life-threatening complication of bilateral adrenalectomy in patients with refractory Cushing’s disease that is caused by the development of an ACTH-secreting tumor in the pituitary gland. Whether USP8 alterations are also present in Nelson’s tumors has not been studied in detail so far....

ea0037oc12.2 | Pituitary – Clinical | ECE2015

The ubiquitin-specific protease 8 gene is frequently mutated in adenomas causing Cushing's disease

Rivas Luis Gustavo Perez , Theodoropoulou Marily , Ferrau Francesco , Nusser Clara , Kawaguchi Kohei , Stratakis Constantine , Faucz Fabio Rueda , Wildemberg Luiz Eduardo , Assie Guillaume , Beschorner Rudi , Stalla Gunther , Buchfelder Michael , Popovic Vera , Honneger Jurgen , Bertherat Jerome , Gadelha Monica R , Beuschlein Felix , Komada Masayuki , Korbonits Marta , Reincke Martin

We have recently reported that somatic mutations in the ubiquitin-specific protease 8 (USP8) are present in corticotropinomas of patients with Cushing’s disease and that these mutations reduced the interaction with 14-3-3. Mutant USP8 exhibited higher deubiquitination activity and potentiated EGFR-induced POMC expression (Reincke et al., Nat Genet 2014). To further study the prevalence of these mutations, we have analyzed 134 ACTH-producing corticotropin...