Searchable abstracts of presentations at key conferences in endocrinology

ea0049p3 | Update on regulation of steroidogenesis by aberrant hormone receptors | ECE2017

Update on regulation of steroidogenesis by aberrant hormone receptors

Lacroix Andre

The mechanisms regulating cortisol production when ACTH of pituitary origin is suppressed in primary adrenal causes of Cushing’s syndrome (CS) include diverse genetic and molecular mechanisms. These can lead either to constitutive activation of the cAMP system and steroidogenesis or to its regulation exerted by the aberrant adrenal expression of several hormone receptors, particularly G-protein coupled hormone receptors (GPCR) and their ligands. Screening for aberrant exp...

ea0041gp153 | Pituitary - Clinical | ECE2016

Once-monthly injection of pasireotide LAR reduces urinary free cortisol (UFC) levels in patients with Cushing’s disease: Results from a randomised, multicentre, phase III trial

Newell-Price John , Petersenn Stephan , Biller Beverly M K , Roughton Michael , Ravichandran Shoba , Lacroix Andre

Background: Twice-daily formulation of pasireotide, a pituitary-directed therapy, is approved for treatment of Cushing’s disease. Here we present data from a phase III study designed to evaluate the more convenient once-monthly long-acting release (LAR) formulation of pasireotide (approved for acromegaly) in patients with Cushing’s disease.Methods: Patients with persistent, recurrent, or de novo Cushing’s disease (not candidates for surger...

ea0081p405 | Pituitary and Neuroendocrinology | ECE2022

Impact of urinary and late-night salivary cortisol levels on clinical signs of hypercortisolism and quality of life in patients with Cushing’s disease treated with osilodrostat

Newell-Price John , Fleseriu Maria , Pivonello Rosario , Feelders Richard , Lacroix Andre , Auchus Richard , Piacentini Andrea , Pedroncelli Alberto , M.K. Biller Beverly

Background: 24-h mean urinary free cortisol (mUFC) and late-night salivary cortisol (LNSC) levels are complementary parameters recommended for screening and monitoring treatment response in patients with Cushing’s disease (CD). In the published core period of the Phase III LINC 3 study (NCT02180217), therapy with osilodrostat (potent oral 11β-hydroxylase inhibitor) produced rapid, sustained reductions in mUFC and LNSC alongside improvements in clinical signs of hyper...

ea0049ep1039 | Pituitary - Clinical | ECE2017

Monthly pasireotide provides clinical benefit over 12 months in patients with Cushing’s disease

Pivonello Rosario , Bronstein Marcello , Schopohl Jochen , Delibasi Tuncay , Barkan Ariel , Suzaki Nori , Tauchmanova Libuse , Gupta Pritam , Petersenn Stefan , Lacroix Andre

Introduction: A monthly, long-acting formulation of pasireotide normalized or reduced mean urinary free cortisol (mUFC) in most patients with Cushing’s disease (CD) in a multicentre, double-blind, Phase III study. The effects of long-acting pasireotide on signs and symptoms of CD are reported here.Methods: Patients with persistent/recurrent (n=123) or de novo (non-surgical candidates; n=27) CD and mUFC≥1.5–5xULN...

ea0037gp.22.04 | Pituitary–Therapy of Cushing's disease | ECE2015

Long-term (5 years) treatment of Cushing's disease with pasireotide

Petersenn Stephan , Salgado Luiz R , Schopohl Jochen , Portocarrero-Ortiz Lesly , Arnaldi Giorgio , Lacroix Andre , Ravichandran Shoba , Kandra Albert , Bagulho Teresa , Biller Beverly MK

Background: In a large 12-month Phase III study, pasireotide led to rapid and sustained decreases in UFC and provided clinical benefit in patients with Cushing’s disease. Here, we report data following an open-label, open-ended extension.Methods: 162 patients with persistent/recurrent or de novo Cushing’s disease were randomized in the core study. 58 patients with mean UFC≤ULN or clinical benefit at month 12 entered the extension...

ea0032p841 | Pituitary – Clinical (<emphasis role="italic">Generously supported by IPSEN</emphasis>) | ECE2013

The benefits of pasireotide in patients with Cushing's disease are not restricted to patients with normalisation of UFC; results from a large, 12-month study

Pivonello Rosario , Petersenn Stephan , Gu Feng , Trovato Andrew , Hughes Gareth , Ligueros-Saylan Monica , Roberto Salgado Luiz , Lacroix Andre , Schopohl Jochen , Biller Beverly

Introduction: Pasireotide normalized or reduced UFC in patients with Cushing’s disease in a large, 12-month study. This analysis evaluates the effects of pasireotide on the signs/symptoms of Cushing’s disease according to the degree of UFC control.Methods: Adult patients (n=162) with persistent/recurrent or de novo Cushing’s disease were randomized to pasireotide 600/900 μg s.c. bid. Dose titration (max: 1200 μg...

ea0056oc12.4 | Novel aspects of puberty development and Cushing's disease | ECE2018

Late-night salivary cortisol (LNSC) levels in a Phase III study of long–acting pasireotide in patients with Cushing’s disease (CD)

Newell-Price John , Pivonello Rosario , Tabarin Antoine , Fleseriu Maria , Witek Przemyslaw , Gadelha Monica , Petersenn Stephan , Tauchmanova Libuse , Ravichandran Shoba , Roughton Michael , Lacroix Andre , Biller Beverly MK

Introduction: LNSC has shown high sensitivity and specificity for the initial diagnosis of CD and detection of disease recurrence; however, the use of LNSC to monitor medical treatment of CD is not well established. The results of an exploratory analysis evaluating changes in LNSC in CD patients receiving long-acting pasireotide during a Phase III study (CSOM230G2304; Lacroix et al. Lancet Diabetes Endocrinol 2018) are reported here.Methods: Pat...

ea0056gp205 | Pituitary Clinical | ECE2018

Predictors of response to long-acting pasireotide in patients with Cushing’s disease during a Phase III study

Witek Przemyslaw , Biller Beverly M K , Lacroix Andre , Feelders Richard , Li Yiming , Geer Eliza B , Brue Thierry , Ravichandran Shoba , Tauchmanova Libuse , Roughton Michael , Petersenn Stephan

Introduction: Long-acting pasireotide reduced urinary free cortisol (UFC) in most patients with Cushing’s disease (CD) during a large Phase III study (Lacroix et al. Lancet Diabetes Endocrinol 2018). The analyses presented here explored the impact of baseline characteristics on response to long-acting pasireotide.Methods: 150 patients with persistent, recurrent or de novo CD and mean UFC (mUFC; from three 24-hour samples collected ...

ea0063oc3.1 | Cushing's and acromegaly | ECE2019

Osilodrostat provides clinical benefit over 48 weeks in patients with Cushing disease: Results from the LINC 3 study

Pivonello Rosario , Fleseriu Maria , Newell-Price John , Bertagna Xavier , Findling James , Shimatsu Akira , Gu Feng , Auchus Richard , Leelawattana Rattana , Jig Lee Eun , Hee Kim Jung , Lacroix Andre , Laplanche Audrey , O'Connell Paul , M Pedroncelli Alberto , Tauchmanova Libuse , MK Biller Beverly

Introduction: Osilodrosat is a potent oral 11β-hydroxylase inhibitor. During the 24-week, single-arm, open-label period of the Phase III LINC 3 study (NCT02180217), osilodrostat treatment demonstrated rapid, sustained reduction in mean urinary free cortisol (mUFC) in most Cushing disease (CD) patients. In the subsequent 8-week, double-blind, randomized-withdrawal phase, a significantly higher proportion of patients receiving osilodrostat maintained normal mUFC at week (W)...

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 ...