Endocrine Abstracts

Corticotroph Pituitary Neuroendocrine Tumours (Co-PitNETs) show significant differences in cortisol secretion, responses to existing therapies and gene expression andstill pose a challenge for patient management.Aim: to explore possible novel therapeutic targets in Co-PitNETs (functioning and silent) through transcriptome analysis (RNA sequencing) and immunohistochemistry. Methods: Transcriptomic data from a previously reported dat...

PAM encodes a multifunctional protein recognized as an important regulator of hormone amidation and secretion. Since PAM germline mutations have been recently identified in patients with PitNETs, it has been proposed as a candidate gene associated with pituitary hypersecretion.Aim: To characterize PAM expression in a large cohort of PitNETs through immunohistochemistry and transcriptome analysis (RNA sequencing).M...

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...

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...

The effective treatment and optimal prognosis of hypercortisolism (Cushing’s syndrome – CS) depend on accurate and early diagnosis. However, hormonal assays can be complex, requiring multiple tests, and not predictive for any related complications, neither for their duration and severity. Identifying novel, specific and easily measurable biomarkers may improve CS diagnosis as well as the evaluation of complications. Since stress-associated epigenetic markers can be...

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...

Background: Constitutional duplications of the PRKACA gene locus have been described as responsible for adrenal Cushing’s disease.The objective here was to evaluate the results of its systematic screening in bilateral adrenal nodular disease and to specify the associated phenotype.Methods: Between 2020 and 2023, 440 consecutive index cases with macronodular or micronodular adrenal hyperplasia or Carney Complex (CNC) w...

An initial multi-omics analysis of PitNETs has refined histological classifications, and could improve diagnostic and prognostic assessment (Neou, Cancer Cell 2020). Of all omics, transcriptome best discriminates between these different classes. This molecular classification has been built upon frozen samples, which are difficult to use in routine clinical practice.Aim: Demonstrate the feasibility of measuring the transcriptome in Formalin-Fixed Paraffin...

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...