Endocrine Abstracts

Introduction: We have previously identified (using a whole-genome large scale SNP- screening approach) germline inactivating stop codon mutations of the PDE11A4 in patients with Cushing syndrome due to micronodular adrenal hyperplasia. PDE11A4 is a cAMP/cGMP phosphodiesterase.Aim of the study: To investigate the role of PDE11A genetic alterations in a large cohort of ACT.Materials and methods: Leukocyte DNA from 117 adrenocortical ...

IntroductionFasting trial remains the gold standard to confirm the diagnosis of insulinoma, based on low blood glucose level concomitant with inadequate high insulin level. However, diagnostic criteria are not consensual. Glycemia and insulin thresholds differ between the different consensus statements : endogenous hyperinsulism diagnosis relies on a glycemia < 3 mmol/l associated with an insulin level > 3 mUI/l in Endocrine Society guidelines (2009)...

IntroductionPheochromocytoma might be associated with hypercortisolism and post-operative adrenal insufficiency. The aim of this study is to determine the frequency of cortisol dysregulation before and after pheochromocytoma surgery.MethodsSingle center retrospective study of consecutive pheochromocytoma patients investigated in the Endocrinology department of Cochin Hospital before and after surgery from 200...

Background: Cushing’s syndrome (CS) is associated with high morbidity and presents high interindividual variability. Easily measurable biomarkers, in addition to the hormone assays currently used for diagnosis, could better quantify the individual biological impact of glucocorticoids. The aim of this study is to identify such biomarkers through the analysis of whole blood transcriptome.Methods: Whole blood transcriptome was evaluated in 57 samples (...

Objective: Large response of steroids precursors, including 17-hydroxyprogesterone and 11-deoxycortisol, to ACTH has been described in adrenocortical tumors, suggesting the existence of intra-tumoral enzymatic deficiencies. This study aimed to compare steroidogenic enzymes activity in unilateral and bilateral benign tumors using serum steroid profiling in HPLC-MS/MS in basal state and after ACTH 1-24 stimulation.Design and Methods: A serum profile of sev...

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...

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...

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...