Searchable abstracts of presentations at key conferences in endocrinology

ea0090p291 | Adrenal and Cardiovascular Endocrinology | ECE2023

ARMC5 regulates SIRT1 expression in adrenocortical cells

Berthon Annabel , Fabio Faucz , Benjamin Feldman , Ludivine Drougat , Stephanie Espiard , Bertherat Jerome , Stratakis Constantine

Pathogenic ARMC5 variants are the main genetic cause of Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) explaining roughly 20% of index cases. These variants found both at germline and somatic level are mostly frameshift and nonsense leading to a loss of its function. ARMC5 acts then, as a tumor suppressor gene but little was initially known on its function. Using an RNAseq analysis on transient zebrafish models of Armc5 up- and d...

ea0041gp25 | Adrenal (2) | ECE2016

Novel genetic changes in Autosomal dominant, ACTH independent nacronodular adrenal hyperplasia associated with hypercortisolism and giant adrenals

Munter Gabriel , Altarescu Geona , Beeri Rachel , Berthon Annabel , Faucz Fabio Rueda , Weiss Ruchama , Stratakis Constantine

ACTH independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing’s syndrome. Both Phosphodiesterase 11A4 (PDE11A4) mutations and inactivating mutations of armadillo repeat containing 5(ARMC5) have been associated with familial AIMAH. A family with autosomal dominant AIMAH was studied trying to elucidate the involved genetic basis.Methods and results: Adrenal hypercortisolism with giant bilateral AH was diagnosed in three adult me...

ea0081p13 | Adrenal and Cardiovascular Endocrinology | ECE2022

ARMC5 as a possible regulator of acetylation in the adrenal cortex in partnership with SIRT1

Berthon Annabel , Faucz Fabio , Feldman Benjamin , Drougat Ludivine , espiard Stephanie , Pontes Cavalcante Isadora , Ragazzon Bruno , Bertherat Jerome , Stratakis Constantine

ARMC5 is a tumor suppressor gene responsible for 20 to 40% of Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) with a function that remains unclear. Based on pathway analysis from RNAseq results obtained on zebrafish models of transient Armc5 up- and down-regulation, we identified transcriptional alterations of several members of SIRT1 (sirtuin (silent mating type information regulation 2 homolog) 1) signaling in our models and hypothesized that ARM...

ea0049gp236 | Thyroid Cancer & Thyroid Case Reports | ECE2017

A rare case of medullary thyroid cancer, mesothelioma and meningioma, due to APC and RASAL1 mutations

Lyssikatos Charalampos , Quezado Martha M , Faucz Fabio R , Angelousi Anna , Nasiri-Ansari Narjes , Stratakis Constantine A , Kassi Eva

Introduction: Patients with “mixed” phenotypes are common among patients with multiple endocrine and non-endocrine neoplasias. Their diagnoses do not fit a given pattern making ge netic counseling difficult and testing impossible to guide. Most of these patients end up getting genome-wide studies for the identification of any predisposing genetic defect. We present a rare case of a 57 year old female who presented clinically with medullary thyroid cancer (MTC), mesot...

ea0056oc10.3 | Cardiovascular aspects of endocrine diseases | ECE2018

ARMC5 variants and risk of hypertension in African Americans: Minority Health-GRID study

Zilbermint Mihail , Gaye Amadou , Berthon Annabel , Hannah-Shmouni Fady , Faucz Fabio , Minority Health-GRID Network Fabio , Davis Adam , Gibbons Gary , Lodish Maya , Stratakis Constantine

Context: Hypertension is one of the most preventable risk factors for cardiovascular disease and death. Up to 42.1% of non-Hispanic African-American subjects have hypertension. We recently found that germline ARMC5 variants may play a role in primary aldosteronism, particularly in African-Americans.Objective: We investigated a cohort of participants in the Minority Health Genomics and Translational Research Bio-Repository Database (MH-GRID) stud...

ea0037oc1.1 | Adrenal 1 | ECE2015

PRKACA defects and cortisol-producing lesions of the adrenal cortex: specific clinical phenotypes and histological features

Angelousi Anna , Salpea Paraskevi , Faucz Fabio , Zilbermint Michail , London Edra , Libe Rossella , Espiard Stephanie , Lyssikatos Charalampos , Kelestimur Fahrettin , Kebebew Electron , Delemer Brigitte , Hieronimus Sylvie , Feve Bruno , Raverot Gerald , Bertherat Jerome , Stratakis Constantine

Introduction: Germline inactivating mutations of the protein kinase A (PKA) regulatory subunit RIα (the PRKAR1A gene) cause primary pigmented nodular adrenocortical disease (PPNAD); other cyclic AMP (cAMP) signalling defects have been associated with bilateral adrenocortical hyperplasia (BAH), cortisol-producing adenoma (CPA) and related lesions. Recently, PRKACA somatic mutations were detected in single, sporadic CPAs in approximately 40% of patients wi...

ea0037s11.1 | Hot topics and IESP symposia | ECE2015

X-linked acro-gigantism (X-LAG): a new form of infant-onset pituitary gigantism

Trivellin Giampaolo , Daly Adrian F. , Faucz Fabio R. , Yuan Bo , Rostomyan Liliya , Larco Darwin O. , Bjelobaba Ivana , Leal Leticia F. , Schernthaner-Reiter Marie Helene , Dimopoulos Aggeliki , Chittiboina Prashant , Choong Catherine S. , Kamenicky Peter , Wu T. John , Costanzi Stefano , Feldman Benjamin , Stojilkovic Stanko S. , Lupski James R. , Beckers Albert , Stratakis Constantine A.

Introduction: Pituitary gigantism is a rare disorder caused by GH-secreting lesions.Aim: We studied gigantism for genetic defects.Methods: We performed genome-wide analyses in 46 patients with gigantism and 248 patients with acromegaly.Results: We detected a novel microduplication at chromosome Xq26.3 in two unrelated kindreds and 13 sporadic cases de novo. All patients had disease onset before five ...

ea0037oc12.2 | Pituitary – Clinical | ECE2015

The ubiquitin-specific protease 8 gene is frequently mutated in adenomas causing Cushing's disease

Rivas Luis Gustavo Perez , Theodoropoulou Marily , Ferrau Francesco , Nusser Clara , Kawaguchi Kohei , Stratakis Constantine , Faucz Fabio Rueda , Wildemberg Luiz Eduardo , Assie Guillaume , Beschorner Rudi , Stalla Gunther , Buchfelder Michael , Popovic Vera , Honneger Jurgen , Bertherat Jerome , Gadelha Monica R , Beuschlein Felix , Komada Masayuki , Korbonits Marta , Reincke Martin

We have recently reported that somatic mutations in the ubiquitin-specific protease 8 (USP8) are present in corticotropinomas of patients with Cushing’s disease and that these mutations reduced the interaction with 14-3-3. Mutant USP8 exhibited higher deubiquitination activity and potentiated EGFR-induced POMC expression (Reincke et al., Nat Genet 2014). To further study the prevalence of these mutations, we have analyzed 134 ACTH-producing corticotropin...

ea0035oc2.2 | Adrenal clinical | ECE2014

Constitutive activation of PRKACA in adrenal Cushing’s syndrome

Beuschlein Felix , Fassnacht Martin , Assie Guilaume , Calebiro Davide , Stratakis Constantine A. , Osswald Andrea , Ronchi Cristina L. , Wieland Thomas , Sbiera Silviu , Faucz Fabio R. , Schaak Katrin , Schmittfull Anett , Kisker Caroline , Diener Susanne , Meitinger Thomas , Lohse Martin J. , Reincke Martin , Bertherat Jerome , Strom Tim M. , Allolio Bruno

Background and Methods: Corticotropin-independent Cushing’s syndrome is caused by tumors or hyperplasia of the adrenal cortex. The molecular pathogenesis of cortisol producing adrenal adenomas is not well understood. Therefore, exome sequencing was performed in 10 cortisol-producing adenomas and recurrent mutations in candidate genes were evaluated in additional 171 patients with adrenocortical tumors. In addition, genome-wide copy number analysis was performed in 35 pati...