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17th European Congress of Endocrinology

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...

ea0037oc1.2 | Adrenal 1 | ECE2015

Functional study of ARMC5 (armadillo repeat containing 5), a new tumour suppressor gene involved in primary bilateral macronodular adrenal hyperplasia

Drougat ludivine , Espiard Stephanie , Doly Stephane , Rodriguez Stephanie , Rizk-Rabin Marthe , Libe Rossella , Assie Guillaume , Marullo Stefano , Ragazzon Bruno , Bertherat Jerome

Introduction: Primary bilateral macronodular adrenal hyperplasia (PBMAH) are adrenocortical tumors leading to adrenal Cushing’s syndrome. Recently, our laboratory has identified the first gene predisposing frequently to PBMAH in adults, named ARMC5 (Armadillo Repeat Containing 5)1. The ARMC5-inactivating mutations identified in leucocyte and tumour DNA in PBMAH patients suggest that ARMC5 is a tumour suppressor gene. However, the mechanisms of action of ARMC5 remain unkno...

ea0037oc1.3 | Adrenal 1 | ECE2015

[123/131I] azetidinylamide a novel radiotracer for diagnosis and treatment of adrenocortical tumours -- from bench to bedside

Hahner Stefanie , Heinze Britta , Herrmann Ken , Buck Andreas K , Blumel Christina , Hanscheid Heribert , Brumberg Joachim , Michelmann David , Nannen Lukas , Ries Martin , Fassnacht Martin , Allolio Bruno , Schirbel Andreas

Background: We have recently introduced [123/131I]iodometomidate (IMTO) which selectively binds to the adrenocortical enzymes aldosterone synthase and 11ß-hydroxylase as SPECT tracer. IMTO has been proven to be useful for molecular adrenal imaging and radiotherapy in adrenal cancer (ACC). As IMTO is rapidly inactivated by endogenous esterases which may impair target tissue to background activity and therapeutic efficacy, >50 new IMTO derivatives have been d...

ea0037oc1.4 | Adrenal 1 | ECE2015

11C-metomidate PET-CT in primary aldosteronism: five possible indications for a non-invasive alternative to adrenal vein sampling

Powlson Andrew S , Koulouri Olympia , Azizan Elena , Maniero Carmela , Taylor Kevin , Aigbirhio Franklin , Koo Brendan , Cheow Heok K , Buscombe John , Gurnell Mark , Brown Morris J

Background: Adrenal vein sampling (AVS) remains the gold-standard for distinguishing unilateral and bilateral disease in primary aldosteronism (PA). However, it is invasive, technically demanding, and may yield inconclusive or equivocal results. 11C-Metomidate PET-CT (11C-MTO-PET-CT) is a non-invasive alternative to AVS for localising unilateral aldosterone-producing adenomas (APAs).Methods/patients: We report a retrospective analys...

ea0037oc1.5 | Adrenal 1 | ECE2015

Norepinephrine transporter as a predictive marker of response to PI3K/mTOR inhibition in phaeochromocytoma

Lee Misu , Laitinen Iina , Braren Rickmer , Pellegata Natalia S

Currently, no effective medical therapy exists for inoperable phaeochromocytomas (PCCs). Thus, we investigated the antitumor potential of the dual PI3K/mTOR inhibitor NVP-BEZ235 against PCC in vivo. We employed a spontaneous model of endogenous aggressive PCCs (MENX rats), which closely recapitulate the human tumours. Administration of NVP-BEZ235 to MENX rats for 14 days inhibited proliferation (assessed by Ki67, NuSAP staining), vascularity (CD31, VEGFA), and induced...