Searchable abstracts of presentations at key conferences in endocrinology

ea0037gp.04.02 | Steroids | ECE2015

The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure

Sherlock Mark , Behan Lucy Ann , Hannon Mark , Alonso Aurora Aragon , Thompson Christopher , Murray Robert , Crabtree Nicola , Hughes Beverly , Arlt Wiebke , Agha Amar , Toogood Andrew , Stewart Paul M

Context: Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate around the optimum glucocorticoid replacement therapy.Objective: To assess the effect of glucocorticoid replacement in hypopituitarism on corticosteroid metabolism and its impact on body composition.Design and patients: We assessed the urinary corticosteroid metabolite profile (using gas chromatography/mass spectrometry) and body ...

ea0037gp.04.04 | Steroids | ECE2015

Regulation of lipogenesis in human hepatocytes by androgens, glucocorticoids, and 5α-reductase

Nikolaou Nikolaos , Nasiri Maryam , Parajes Sylvia , Krone Nils , Mastorakos George , Valsamakis George , Hughes Beverly , Taylor Angela , Bujalska Iwona , Gathercole Laura , Tomlinson Jeremy

Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the commonest cause of liver cirrhosis and leading indication for liver transplant worldwide. It is tightly associated with obesity and type 2 diabetes, yet the precise mechanisms that drive its aetiology are not fully defined. Dysregulation of both glucocorticoid and androgen metabolism has been implicated in its pathogenesis. The availability of these hormones to bind and activate their receptors is mainly regulat...

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...

ea0035oc8.4 | Pituitary clinical | ECE2014

Normalization of urinary cortisol with the potent 11β-hydroxylase inhibitor LCI699 in patients with Cushing's disease: 22-week, multicentre, open-label study

Biller Beverly , Young Jacques , Hamrahian Amir , Fleseriu Maria , Molitch Mark , Pivonello Rosario , Shimatsu Akira , Shimizu Chikara , Tanaka Tomoaki , White Tracy , Hilliard Annie , Tian Chuan , Sauter Nicholas , Bertagna Xavier

Background: A proof-of-concept study (LINC 1) demonstrated that after 10 weeks, LCI699 normalized UFC in 11/12 patients with Cushing’s disease. This interim analysis of the first eight patients enrolled into a longer-term study (LINC 2) further evaluates LCI699 in Cushing’s disease; the full analysis on all 19 enrolled patients is expected in time for the congress.Methods: There were two study groups. Previous LINC 1 participants (follow-up coh...

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...

ea0032p907 | Pituitary – Clinical (<emphasis role="italic">Generously supported by IPSEN</emphasis>) | ECE2013

Characteristics and outcomes of the Italian subpopulation enrolled in the observational, multicenter hypopituitary control and complications study (HypoCCS)

Aimaretti Gianluca , Ferone Diego , Ambrosio Maria Rosaria , Beck-Peccoz Paolo , Cannavo Salvatore , Colao Anna Maria , Losa Marco , Martinez Beverly Festin , Marchi Paolo , Vottero Alessandra

Aim: To describe characteristics and outcomes of Italian patients with hypopituitarism participating in HypoCCS.Methods: Study population was stratified by max GH peak (mGHp) and BMI. Baseline variables included demographic characteristics, type of deficit, smoking habits; variables analyzed over time included weight, Framingham cardiovascular disease (CVD) risk, lipids, GH dose.Results: Italian subpopulation included 342 patients ...

ea0016p425 | Neuroendocrinology | ECE2008

Tests of growth hormone (GH) status in severe GH deficiency: do they identify a similar phenotype? Insight from the KIMS database

Toogood Andrew , Brabant George , Buchfelder Michael , Feldt-Rasmussen Ulla , Koltowska-Haggstrom Maria , Jonsson Bjorn , Krogh Rasmussen AEse , Maiter Dominique , Saller Bernhard , Biller Beverly

A GH peak of 3 μg/l during the insulin tolerance test (ITT) is considered the gold standard for identifying adults with severe GH deficiency. Alternative stimuli such as arginine (AST) and glucagon (GST) are also employed but produce lower GH peaks than the ITT in normal subjects. Despite this, 3 μg/l is used as the diagnostic threshold for these tests, raising the possibility that severe GH deficiency is being diagnosed inappropriately.We stud...

ea0015oc16 | Reproduction | SFEBES2008

Enhanced hypothalamic–pituitary–adrenal axis activation, 5α-reductase activity and insulin resistance distinguishes polycystic ovary syndrome from simple obesity

Vassiliadi Dimitra A , Tomlinson Jeremy W , Hughes Beverly A , Gay Christopher , Sira Shaleen , Nightingale Peter , Shackleton Cedric HL , Stewart Paul M , Arlt Wiebke

Polycystic ovary syndrome (PCOS) affects 5–10% of the female population. It is characterised by androgen excess and anovulatory infertility; several studies have reported an increased incidence of the metabolic syndrome and enhanced 5α-reductase activity in PCOS. However, the contribution of obesity to these findings has yet to be clarified. Here we have analysed metabolic status and urinary steroid metabolite excretion in 114 patients with PCOS (median age 30 (range...

ea0013p193 | Diabetes, metabolism and cardiovascular | SFEBES2007

Reduced 11beta-hydroxysteroid dehydrogenase type 1 activity in obese children

Wiegand Susanna , Richardt Anna , Remer Thomas , Wudy Stefan A , Tomlinson Jeremy W , Hughes Beverly , Grüters Annette , Stewart Paul M , Strasburger Christian J , Quinkler Marcus

Objective: The incidence of childhood obesity and type 2 diabetes has reached epidemic proportions. Glucocorticoid excess causes central obesity and diabetes mellitus as seen in Cushing’s syndrome. The 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1), which is predominantly expressed in liver and adipose tissue, regenerates active cortisol from inactive cortisone. Altered 11beta-HSD1 may cause tissue-specific Cushing syndrome with central obesity and impair...

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...