Searchable abstracts of presentations at key conferences in endocrinology

ea0049gp5 | Adrenal 1 | ECE2017

Protein Kinase A signaling saves regulatory subunit IIβ from PRKACA mutation-mediated degradation

Weigand Isabel , Bathon Kerstin , Ronchi Cristina , Rizk-Rabin Marthe , Di Dalmazi Guido , Wild Vanessa , Rubin Beatrice , Vanselow Jens T , Schlosser Andreas , Calebiro Davide , Beuschlein Felix , Bertherat Jerome , Fassnacht Martin , Sbiera Silviu

Protein Kinase A (PKA) consists of two catalytic and two regulatory subunits with several isoforms (Cα,β,γ, RIα,IIα,Iβ,IIβ). In 30–40% of cortisol-producing adrenocortical adenomas (CPA) heterozygous activating somatic mutations in the catalytic subunit α (Cα) of PKA have been found. Previous reports found strikingly reduced levels of RIIβ in CPA compared to other adrenocortical tumors. Here, we investigated the correlatio...

ea0049gp123 | Endocrine Tumours | ECE2017

Outcome of patients with adrenocortical cancer after discontinuation of adjuvant mitotane therapy

Terzolo Massimo , Basile Vittoria , Megerle Felix , Hermann Wiebke , Cicciarella Federica , Libe Rossella , Baudin Eric , Haak Harm , Mannelli Massimo , Boscaro Marco , Quinkler Marcus , Bourdeau Isabelle , Perotti Paola , Hahner Stefanie , Beuschlein Felix , Fassnacht Martin

Background: Adjuvant mitotane therapy is frequently used in Europe following surgery for adrenocortical carcinoma (ACC). Management of adjuvant mitotane is mainly empirical and a major open question is the optimal duration of therapy, because no study has ever addressed this issue.Objective: We aimed to assess the outcome of ACC patients who were treated with adjuvant mitotane for at least one year following surgery and then discontinued therapy for othe...

ea0049ep52 | Adrenal cortex (to include Cushing's) | ECE2017

Characteristics of aldosterone-producing adenomas: a tissue microarray study

Rhayem Yara , Feuchtinger Annette , Woischke Christine , Ludwig Philippe , Kunzke Thomas , Schwarzmayr Thomas , Hahner Stefanie , Gomez-Sanchez Celso E. , Strom Tim M. , Kirchner Thomas , Reincke Martin , Walch Axel , Beuschlein Felix

Background: Sporadic aldosterone-producing adenomas (APA) are relevant cause of endocrine related hypertension in Primary Aldosteronism (PA). Next generation sequencing techniques have identified somatic mutations in APA harbored in KCNJ5, ATP1A1, ATP2B3, CACNA1D, CTNNB1 and PRKACA genes. Yet, a number of APA harbor no mutations in candidate genes (designated as wild type, WT) and little is known about genotype/phenotype correlation.Objectives: We invest...

ea0041gp9 | Adrenal | ECE2016

Is steroid profiling using LC-MS/MS useful in the diagnostic work-up of primary aldosteronism?

Williams Tracy A. , Lenders Jacques W.M. , Peitzsch Mirko , Dekkers Tanja , Dietz Anna S. , Rump Lars C. , Willenberg Holger S. , Treitl Marcus , Bidlingmaier Martin , Beuschlein Felix , Deinum Jaap , Eisenhofer Graeme , Reincke Martin

Introduction: Primary aldosteronism (PA) is mainly caused by unilateral aldosterone-producing adenomas (APA) or bilateral adrenal hyperplasia (BAH). Subtype differentiation relies on the invasive and technically challenging adrenal venous sampling (AVS). We recently demonstrated the potential utility of peripheral plasma steroid profiling by LC-MS/MS to distinguish APA and BAH. We tested the following hypotheses: first, if steroid profiling in combination with AVS, effectively...

ea0041gp10 | Adrenal | ECE2016

PRKACA somatic mutations are rare in aldosterone-producing adenomas.

Rhayem Yara , Perez-Rivas Luis Gustavo , Dietz Anna , Bathon Kerstin , Gebhard Christian , Riester Anna , Mauracher Brigitte , Gomez-Sanchez Celso , Schwarzmayr Thomas , Calebiro Davide , Strom Tim M. , Reincke Martin , Beuschlein Felix

Aldosterone-producing adenomas (APAs) are the most frequent cause of primary aldosteronism (PA). Somatic mutations of KCNJ5, ATP1A1, CACNA1D and ATP2B3 are involved in APAs formation while CTNNB1 and GNAS somatic mutations have been described in both APAs and in cortisol-producing adenomas (CPAs). In contrast, mutations of PRKACA coding for the catalytic subunit of protein kinase A have been yet only identified in ...

ea0038oc1.6 | Early Career Oral Communications | SFEBES2015

Urine steroid metabolomics as a diagnostic tool in primary aldosteronism

Lang Katharina , Beuschlein Felix , Biehl Michael , Dietz Anna , Riester Anna , Hughes Beverly A , O'Neil Donna M , Hahner Stefanie , Quinkler Marcus , Lenders Jacques W , Shackleton Cedric H L , Reincke Martin , Arlt Wiebke

Introduction: The regular diagnostic workup for primary aldosteronism (PA) can be very demanding and involves multiple invasive as well as time and cost intensive diagnostic tests. Here we have explored the value of urinary steroid metabolome analysis in the diagnosis and differential diagnosis of PA. Previously, urinary 3α,5β-tetrahydroaldosterone (THAldo) has been suggested as a reliable screening test for PA and serum 18-oxocortisol and 18-hydroxycortisol have bee...

ea0038oc3.4 | Steroids and adrenal | SFEBES2015

Urine steroid metabolomics as a novel diagnostic tool for early detection of recurrence in adrenocortical carcinoma

Chortis Vasileios , Bancos Irina , Lang Katharina , Hughes Beverly , O'Neil Donna , Taylor Angela , Fassnacht Martin , Bertherat Jerome , Beuschlein Felix , Quinkler Marcus , Vassiliadi Dimitra , Dennedy M Conall , Mannelli Massimo , Biehl Michael , Arlt Wiebke

Introduction: Adrenocortical carcinoma (ACC) is an aggressive malignancy with a high rate of recurrence. Regular post-operative follow-up imaging is necessary, but associated with high radiation exposure and frequent diagnostic ambiguity. Urine steroid metabolomics has recently been introduced as a novel diagnostic tool for the detection of adrenocortical malignancy in patients with adrenal incidentalomas. Here we present the first clinical study assessing the performance of t...

ea0035p7 | Adrenal cortex | ECE2014

Favorable long-term outcome of bilateral adrenalectomy in Cushing's disease

Osswald Andrea , Plomer Eva , Dimopoulou Christina , Milian Monika , Blaser Rainer , Ritzel Katrin , Mickisch Anne , Knerr Ferengis , Stanojevic Milan , Hallfeldt Klaus , Schopohl Jochen , Kuhn Klaus A , Stalla Gunter , Beuschlein Felix , Reincke Martin

Objective: Bilateral adrenalectomy (BADX) is an important treatment option for patients with Cushing’s syndrome (CS). The outcome of this procedure has not been studied well.The aim was to analyze long-term outcome of CS patients treated with BADX.Design: Fifty patients with BADX treated since 1990 in two German centers were identified. 34 patients had Cushing’s disease (CD), nine ectopic Cushing-syndrome (ECS), and seven...

ea0070yi3 | Young Investigators | ECE2020

RNA-sequencing of adrenocortical tumors reveals novel pathogenetic insights

Di Dalmazi Guido , Altieri Barbara , Scholz Claus , Sbiera Silviu , Luconi Michaela , Waldmann Jens , Kastelan Darko , Ceccato Filippo , Chiodini Iacopo , Arnaldi Giorgio , Osswald Andrea , Reincke Martin , Beuschlein Felix , Sauer Sascha , Fassnacht Martin , Appenzeller Silke , Ronchi Cristina

Background: Genetic alterations underlying the pathogenesis of autonomous cortisol secretion and early adrenocortical tumorigenesis have been identified in 40% of adrenocortical tumors (ACT). Nonetheless, the molecular events leading to development of ACT and steroid secretion remain obscure for a large proportion of patients.Aim: Aims of our study were to investigate the relationship between transcriptome profile and genetic background in a large series...

ea0070aep565 | Pituitary and Neuroendocrinology | ECE2020

Hypercortisolism-related molecular signature: Results from whole blood methylome analysis

Armignacco Roberta , Septier Amandine , Jouinot Anne , Neou Mario , Gaspar Cassandra , Perlemoine Karine , Bouys Lucas , Braun Leah , Riester Anna , Zennaro Maria-Christina , Reincke Martin , Bertherat Jérôme , Beuschlein Felix , Assié Guillaume

The effective treatment and optimal prognosis of hypercortisolism (Cushing’s syndrome – CS) depend on accurate and early diagnosis. However, hormonal assays can be complex, requiring multiple tests, and not predictive for any related complications, neither for their duration and severity. Identifying novel, specific and easily measurable biomarkers may improve CS diagnosis as well as the evaluation of complications. Since stress-associated epigenetic markers can be...