Searchable abstracts of presentations at key conferences in endocrinology

ea0063oc10.4 | Adrenal 2 | ECE2019

Cullin 3 is a partner of armadillo repeat containing 5 (ARMC5), the product of the gene responsible for primary bilateral macronodular adrenal hyperplasia

Cavalcante Isadora , Vaczlavik Anna , Drougat Ludivine , Lotfi Claudimara , Fragoso Maria , Clauser Eric , Rizk-Rabin Marthe , Bertherat Jerome , Ragazzon Bruno

Background: Germline mutations of ARMC5 (Armadillo repeat containing 5 gene) were identified as a frequent cause of primary bilateral macronodular adrenal hyperplasia (PBMAH). ARMC5 is considered as a tumor suppressor gene regulating apoptosis and steroidogenesis by unknown mechanisms. The ARMC5 protein contains a N-terminal domain made of Armadillo (ARM) repeats and a C-terminal ‘Bric-a-Brac, Tramtrack, Broad-complex/Pox virus and Zinc finger (BTB/POZ)&...

ea0049gp6 | Adrenal 1 | ECE2017

Involvement of ARMC5 in proliferation and cell cycle control of human cell cultures from adrenal nodules of primary macronodular adrenocortical hyperplasia (PMAH)

Cavalcante Isadora , Nishi Mirian , Zerbini Maria Claudia , Chambo Jose Luiz , Almeida Madson , Lotfi Claudimara , Fragoso Maria Candida

Background: The mechanisms causing hypercortisolism in primary macronodular adrenocortical hyperplasia (PMAH) are not fully clarified. The participation of ectopic receptors and autocrine/paracrine regulation of intra-adrenal ACTH in hyperplastic tissue have been considered. Additionally, germline ARMC5 mutations have been described as main cause of PMAH. So far, the functional study that analyzed the role of ARMC5 used the adrenocortical carcinoma cell line, H295R. T...

ea0056oc5.5 | Diving deep into adrenal cortex diseases | ECE2018

Cullin 3 is a partner of Armadillo Repeat Containing 5 (ARMC5), the product of the gene responsible for Primary Bilateral Macronodular Adrenal Hyperplasia

Cavalcante Isadora , Clauser Eric , Vaczlavik Anna , Drougat Ludivine , Lotfi Claudimara , Fragoso Maria , Rizk-Rabin Marthe , Bertherat Jerome , Ragazzon Bruno

Background: ARMC5 (armadillo repeat containing 5) has been identified as the gene responsible for PBMAH (Primary Bilateral Macronodular Adrenal Hyperplasia). ARMC5 inactivating mutations are reported in 20 to 25% of PBMAH patients. ARMC5, is considered as a tumor suppressor gene controlling apoptosis and regulating steroidogenesis. The mechanisms of action of ARMC5 are unknown. The structure of the ARMC5 protein contains ARM repeats and a BT...

ea0063oc10.3 | Adrenal 2 | ECE2019

Genetic predisposition to Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH): next generation sequencing ARMC5, NR3C1 (glucocorticoid receptor) and PDE11A4 (phosphodiesterase 11) in 389 patients

Vaczlavik Anna , Vaduva Patricia , Bouys Lucas , Neou Mario , Septier Amandine , Heurtier Victor , Libe Rossella , Kroiss Matthias , Borson-Chazot Francoise , Chanson Philippe , Vanthyghem Marie-Christine , Tabarin Antoine , Assie Guillaume , Stratakis Constantine , Fragoso Maria , Ragazzon Bruno , Bertherat Jerome

Introduction: PBMAH is an heterogeneous disease from the clinical, hormonal, and morphological point of view. ARMC5 inactivating mutations have been reported as a cause of PBMAH. PDE11A4 variants have been associated with PBMAH and NR3C1 variants with bilateral adrenal incidentalomas.Aim: To analyse the frequency of ARMC5 pathogenic mutations and PDE11A4 and NR3C1 variants in PBMAH patients.<p cla...

ea0070oc7.3 | Endocrine-related Cancer | ECE2020

Sterol O-Acyl transferase 1 as a prognostic marker of adrenocortical carcinoma

Ferreira Lacombe Amanda M , Cauduro Soares Ibere , Bezerra-Neto João Evangelista , da Silva Charchar Helaine , Hoff Ana O , Almeida Madson Q , Weigand Isabel , Kroiss Matthias , Nogueira Zerbini Maria Claudia , Barisson Villares Fragoso Maria Candida

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis. Despite the poor prognosis in the majority of patients, no improvements in treatment strategies have been achieved. Therefore, the discovery of new prognostic biomarkers is of enormous interest. Sterol-O-acyl transferase 1 (SOAT1) is involved in cholesterol esterification and lipid droplet formation. Recently, it was demonstrated that SOAT1 inhibition leads to impaired steroidogenesis ...

ea0090p558 | Adrenal and Cardiovascular Endocrinology | ECE2023

Description of 38 novel ARMC5 variants and review of the literature: the updated mutational landscape of ARMC5 in Bilateral Macronodular Adrenocortical Disease

Bouys Lucas , Vaczlavik Anna , Pontes Cavalcante Isadora , Violon Florian , Jouinot Anne , Berthon Annabel , Vaduva Patricia , Espiard Stephanie , Perlemoine Karine , Kamenicky Peter , Vantyghem Marie-Christine , Tabarin Antoine , Raverot Gerald , Ronchi Cristina , Dischinger Ulrich , Reincke Martin , Candida Barisson Villares Fragoso Maria , Stratakis Constantine , North Marie-Odile , Pasmant Eric , Ragazzon Bruno , Bertherat Jerome

Introduction: Bilateral Macronodular Adrenocortical Disease (BMAD) is a rare cause of Cushing syndrome due to bilateral adrenocortical macronodules. Germline inactivating variants of the tumor suppressor gene ARMC5 have been described by our group 10 years ago and are responsible for 20-25% of apparently sporadic BMAD cases and 80% of familial presentations. ARMC5 patients present with a more pronounced phenotype than wild-type patients, in terms of cortisol ...

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....

ea0070oc1.6 | Adrenal and Cardiovascular Endocrinology | ECE2020

Modified GRAS score for prognostic classification of adrenocortical carcinoma: an ENSAT multicentre study

Elhassan Yasir , Altieri Barbara , Berhane Sarah , Cook Harriet , Bertherat Jerome , Fragoso Maria , Kastelan Darko , Terzolo Massimo , Calabrese Anna , Berruti Alfredo , Cosentini Deborah , Laganà Marta , Loli Paola , Baudin Eric , Haak Harm , Canu Letizia , Haissaguerre Magalie , Kimpel Otilia , Deeks Jon , Arlt Wiebke , Libé Rossella , Fassnacht Martin , Ronchi Cristina

Background: Adrenocortical carcinoma (ACC) has an aggressive but heterogenous behaviour. ENSAT stage and Ki67 proliferation index are used to predict clinical outcome but are limited in distinguishing patients with best outcome. We aimed to validate the prognostic role of clinical and histopathological parameters alone or combined by applying a previously proposed points-based score (mGRAS, Lippert JCEM 2018) to a large multicentre cohort of ACC patients.<p class="abstext"...

ea0073oc1.3 | Oral Communications 1: Adrenal and Cardiovascular Endocrinology | ECE2021

PDE11A4 (Phosphodiesterase 11 A4) is a modulator of the primary bilateral macronodular adrenal hyperplasia (PBMAH) phenotype: genotype/phenotype analysis of a cohort of 354 patients analysed by next-generation sequencing (NGS)

Vaduva Patricia , Anna Vaczlavik , Lucas Bouys , Neou Mario , Septier Amandine , Heurtier Victor , Cavalcante Isadora Pontes , RossellaLibe , Fabio Faucz , Gaetan Giannone , Kroiss Matthias , Borson-Chazot Francoise , Chanson Philippe , Tabarin Antoine , Marie-Christine Marie-Christine , Assié Guillaume , Candida Barisson Villares Fragoso Maria , Constantine Stratakis , Ragazzon Bruno , Bertherat Jerome

IntroductionPrimary bilateral macronodular adrenal hyperplasia (PBMAH), the most common cause of adrenal Cushing’s syndrome due to bilateral adrenal tumors, is an heterogenous disease with various clinical, hormonal and morphological characteristics. ARMC5 inactivating mutations is the most frequent genetic cause of PBMAH and variants of PDE11A4 have been associated with the disease. In order to better understand the heterogeneity ...

ea0073oc11.5 | Oral Communications 11: Adrenal and Cardiovascular Endocrinoloyg | ECE2021

Results of the ADIUVO trial, the first randomized study on post-operative adjuvant mitotane in patients with adrenocortical carcinoma

Terzolo Massimo , Fassnacht Martin , Perotti Paola , Libè Rossella , Lacroix Andre , Kastelan Darko , R. Haak Harm , Arlt Wiebke , Loli Paola , Decoudier Benedicte , Lasolle Hélène , Bancos Irina , Quinkler Marcus , Barisson Villares Fragoso Maria Candida , Canu Letizia , Puglisi Soraya , Calabrese Anna , Kroiss Matthias , Dusek Tina , Bourdeau Isabelle , Baudin Eric , Berchialla Paola , Beuschlein Felix , Bertherat Jerome , Berruti Alfredo

BackgroundThe ESE-ENSAT guidelines suggest adjuvant mitotane for patients with adrenocortical carcinoma (ACC) at high risk of recurrence following radical surgery. This indication has a limited evidence base, lacking results from randomized controlled trials. No suggestion is available in low-risk patients, since studies did not stratify patients for prognosis. The randomized controlled study ADIUVO compared the efficacy of adjuvant mitotane (MIT) treatm...