Searchable abstracts of presentations at key conferences in endocrinology

ea0041ep736 | Neuroendocrinology | ECE2016

The medical treatment with pasireotide in Cushing’s disease: an Italian multicenter experience based on “Real Word Evidence”

Pivonello Rosario , Arnaldi Giorgio , Scaroni Carla Maria , Giordano Carla , Cannavo Salvatore , Iacuaniello Davide , Trementino Laura , Zilio Marialuisa , Guarnotta Valentina , Albani Adriana , Cozzolino Alessia , Michetti Grazia , Boscaro Marco , Colao Annamaria

A recent phase III clinical trial has demonstrated that the treatment with the somatostatin analogue pasireotide normalizes cortisol secretion in 15–28% of patients with Cushing’s disease (CD). The aim of the current study was to evaluate the effectiveness of 6-months pasireotide treatment on clinical and hormonal profiles in a group of CD patients with mild to moderate disease according with the real-word evidence. Thirty-two patients with CD unsuccessfully treated ...

ea0041ep887 | Pituitary - Clinical | ECE2016

Long-term (19-month) control of urinary free cortisol with osilodrostat in patients with Cushing’s disease: results from an extension to the LINC-2 study

Pivonello Rosario , Hatipoglu Betul , Bertagna Xavier , Fleseriu Maria , Molitch Mark E , Shimizu Chikara , Tanaka Tomoaki , Shimatsu Akira , Biller Beverly M K , Ravichandran Shoba , Kandra Albert , Sauter Nicholas , Young Jacques

Introduction: During the 22-week LINC-2 study, the potent oral 11β-hydroxylase inhibitor osilodrostat normalized UFC in 15/19 (78.9%) patients with Cushing’s disease. Most common AEs were nausea, diarrhoea, asthenia, and adrenal insufficiency. This report describes 19-month results following an extension.Methods: Patients who were receiving clinical benefit at week 22 could enter the extension. Efficacy/safety is reported for patients who enter...

ea0035p62 | Adrenal Medulla | ECE2014

Expression of IGF/mTOR pathway components in human pheochromocytomas and in vitro inhibition of PC12 rat pheochromocytoma cell growth by mTOR inhibitors alone and in combination with the dual IGFI-R/INS-R antagonist OSI-906

Martino Maria Cristina De , Feelders Richard A. , Dogan Fadime , Koetsveld Peter M. van , Krijger Ronald R. De , Janssen Joseph A M J L , Sprij-Mooij Diana , Lamberts Steven W. J. , Herder Wouter W de , Colao Annamaria , Pivonello Rosario , Hofland Leo J

The mTOR and IGF pathways have been suggested to play a role in the pathogenesis of pheochromocytomas (PCC). mTOR inhibitors, as sirolimus (S) and everolimus (E), as well as IGF1R antagonists could be a potential novel treatment for malignant PPC.The aim of this study was to evaluate the expression of the main components of the IGF/mTOR pathway in human PCC and to investigate the effects of the mTOR inhibitors S and E and of the IGF1R/insulin receptor (I...

ea0070oc4.5 | Pituitary and Neuroendocrinology | ECE2020

Durability of response and gender-based analysis from the LINC3 trial of osilodrostat in the treatment in cushing’s disease

Pivonello Rosario , Fleseriu Maria , Newell-Price John , Xavier Bertagna , James Findling , Akira Shimatsu , Feng Gu , Richard Auchus , Rattana Leelawattana , Jig Lee Eun , Hee Kim Jung , Andre Lacroix , Biller Beverly

Introduction: In a Phase II study, osilodrostat, a potent oral 11β-hydroxylase inhibitor, normalized mean urinary free cortisol (mUFC) in most patients with CD. We report the efficacy and safety of osilodrostat in a large CD patient population (NCT02180217).Methods: In this study, open-label osilodrostat was initiated at 2 mg bid in 137 adults with CD and mUFC > 1.5 × ULN, with dose adjustments every 2 weeks (range 1–30 mg bid) up to ...

ea0070aep678 | Pituitary and Neuroendocrinology | ECE2020

Levoketoconazole in the treatment of endogenous Cushing’s syndrome: Extended evaluation phase results of the SONICS study

Fleseriu Maria , Auchus Richard J , Greenman Yona , Zacharieva Sabina , Geer Eliza B , Salvatori Roberto , Pivonello Rosario , Feldt-Rasmussen Ulla , Kennedy Laurence , Buchfelder Michael , Biller Beverly M K , Cohen Fredric , Heaney Anthony P

Background: The phase 3, open-label SONICS study of levoketoconazole demonstrated sustained reduction in mean urinary free cortisol (mUFC) in adults with endogenous Cushing’s syndrome (CS). The extended evaluation phase (Ext) of SONICS reported here further assessed long-term safety, tolerability, and benefit/risk of this treatment.Methods: SONICS consisted of dose-titration (150 – 600 mg BID to attain maximally tolerated dose for mUFC normal...

ea0070aep744 | Pituitary and Neuroendocrinology | ECE2020

Pasireotide-induced hyperglycemia and efficacy of antidiabetic treatments in patients with acromegaly: Evaluation of two referral centers

F.S. Grasso Ludovica , Chiloiro Sabrina , Pirchio Rosa , Giampietro Antonella , Auriemma Renata S. , Bianchi Antonio , De Martino Maria Cristina , Negri Mariarosaria , Colao Annamaria , Pontecorvi Alfredo , De Marinis Laura , Pivonello Rosario

Pasireotide (PAS) has a safety profile similar to first-generationsomatostatin analogues (SSA), except for a higher frequency of hyperglycaemia-related adverse events (AEs). However, consensus on the best management of PAS-induced hyperglycaemia in acromegalic patients has still to be defined. The current study aims at investigating the effects of long-term PAS treatment on glucose metabolism, by evaluating the clinical management of hyperglycemia-relatedAEs in acromegalic pat...

ea0032p11 | Adrenal cortex | ECE2013

Molecular screening for personalized treatment approach in advanced adrenocortical cancer

De Martino Maria Cristina , Al Ghuzlan Abir , Do Cao Christine , Assie Guillaume , Scoazec Jean-Yves , Leboulleux Sophie , Aubert Sebastien , Libe Rossella , Nozieres Cecile , Pattou Francois , Borson-Chazot Francoise , Pivonello Rosario , Mazoyer Clement , Bertherat Jerome , Schlumberger Martin , Lacroix Ludovic , Baudin Eric

Propose: To screen for the presence of putative targets for new treatments in a large cohort of advanced adrenocortical cancer (ACC)Experimental design: In 40 adult stage III-IV ACC primary samples, we used comparative genomic hybridization (CGH) and hotspot gene sequencing (with Ion Torrent) to describe the presence of copy number abnormalities and mutations in more than 40 genes involved in cancer development and putative drug sensitivity (HER2; EGFR; ...

ea0032p649 | Male reproduction | ECE2013

Characterization of R31C GNRH1 mutation in congenital hypogonadotropic hypogonadism

Maione Luigi , Albarel Frederique , Bouchard Philippe , Gallant Megan , Flanagan Colleen A , Bobe Regis , Cohen-Tannoudji Joelle , Pivonello Rosario , Colao Annamaria , Brue Thierry , Lombes Marc , Millar Robert P , Young Jacques , Guiochon-Mantel Anne , Bouligand Jerome

Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare reproductive disease leading to lack of puberty and infertility. Loss-of-function mutations of GNRH1 gene are a very rare cause of autosomal recessive nCHH. R31C GNRH1 is the only missense mutation that affects the conserved GnRH decapeptide sequence. This mutation was identified in a CpG islet in nine nCHH subjects from four unrelated families, giving evidence for a putative ‘hot spot&#...

ea0026p363 | Adrenal medulla | ECE2011

Expression of IGF/mTOR pathway components in human pheochromocytomas and in vitro inhibition of PC12 rat pheochromocytoma cell growth by mTOR inhibitors

De Martino M C , Feelders R A , van Koetsveld P M , De Krijger R R , Janssen J A M J L , Sprij-Mooij D , Lamberts S W J , de Herder W W , Colao Annamaria , Pivonello Rosario , Hofland Leo

The pathogenesis of pheochromocytomas (pheo) is poorly understood and malignant pheo need new treatment options. mTOR inhibitors, as sirolimus (S) and everolimus (E), are new promising antineoplastic drugs.Aim: To evaluate whether the IGF/mTOR pathways have a role in the pathogenesis and whether S and E may have antiproliferative effects in pheo.In 24 human pheo and two normal adrenal medulla (NM), we evaluated the mRNA expression ...

ea0022p52 | Adrenal | ECE2010

Expression of mTOR and IGF2 and in vitro effects of mTOR inhibitor drugs on cell proliferation and cortisol production in human adrenocortical cancer cells

De Martino Maria Cristina , van Koetsveld P M , Sprij-Mooij D M , Feelders Richard A , de Herder Wouter W , Lamberts Steven W J , Colao Annamaria , Pivonello Rosario , Hofland Leo J

Background: Adrenocortical carcinoma (ACC) is an uncommon malignancy with a still scantily understood pathogenesis and generally poor prognosis. Many patients with ACC need new treatment options. mTOR inhibitors, as sirolimus (S) and temsirolimus (T), are promising antineoplastic drugs in several kinds of tumors.Methods: In three human ACC cell lines (H295, HAC15 and SW13), we evaluated the mTOR and IGF2 expression at mRNA level (by qPCR) and at protein ...