Endocrine Abstracts

Background: Molecular classification is important for diagnosis and prognosis of adrenocortical tumors (ACT). Transcriptome profiles separate benign ACT (“C2” cluster) from carcinomas (ACC) and identify two groups of ACC, “C1A” (“steroid” and “proliferation” signatures) and “C1B” (“immune” signature), of poor and better prognosis respectively. However, these signatures were characterized at the tissue level (“bul...

Introduction: The gold standard for insulinoma diagnosis is still 72-hours fasting trial with the aim to trigger Whipple’s triad. In this context, biological diagnosis of endogenous hyperinsulinism relies on the occurrence of a hypoglycemia, concomitant with inadequate high insulin and C-peptide levels. However, diagnostic cut-offs are not consensual among the different learned societies (Endocrine Society 2009, NANETS 2010, ENETS 2012). The objective of this wor...

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...

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...

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...

Background: Adrenocortical cancer (ACC) is an aggressive tumor with heterogeneous prognosis. Previous genomic studies have demonstrated the importance of molecular classification for the prognostic assessment. Among molecular markers, transcriptome profiles “C1A” (steroid and proliferative signature) and “C1B” (immune signature) show the strongest association with outcome. However these markers are determined so far only from frozen tissue samples, sinc...

Propose: To screen for the presence of putative targets for new treatments in a large cohort of advanced adrenocortical cancer (ACC)Experimental design: In 40 adult stage III-IV ACC primary samples, we used comparative genomic hybridization (CGH) and hotspot gene sequencing (with Ion Torrent) to describe the presence of copy number abnormalities and mutations in more than 40 genes involved in cancer development and putative drug sensitivity (HER2; EGFR; ...

Benign adrenal tumors correspond to a spectrum of distinct tumors, including uni- and bilateral diseases with distinct morphological features, and various steroid hormone secretion types and levels. The aim is to study this variability at the molecular level using pan-genomic approaches.Methods: One hundred and forty six benign adrenal tumors, including adrenocortical adenomas (ACA, N=), primary macronodular adrenal hyperplasia (PMAH, N=), and primary pi...

Introduction: The steroidogenesis inhibitor osilodrostat (OSI), indicated for the medical treatment of endogenous Cushing’s syndrome, exhibits significant interindividual variability regarding the response to treatment (Pivonello et al. 2020). Plasma exposure may contribute to this variability. Our objective was to investigate the effect of concomitant use of mitotane (MIT), a potent inducer of CYP450 (3A4), on circulating OSI concentrations in patients treated f...

Background: Pheochromocytomas and paragangliomas (mPPGL) are rare neuroendocrine tumors. Therapeutic options in advanced and irresectable mPPGL are limited. Two small retrospective studies demonstrated the effectiveness of temozolomide in patients with mPPGL and suggested that patients with mutation in the succinate dehydrogenase B (SDHB) gene might benefit more than SDHB wildtype cases.Aim: To re-evaluate safety and effectiveness of temozolomide in a la...