Endocrine Abstracts

The 2017 World Health Organization (WHO) classification of pituitary adenomas is based on cell lineage and transcription factors (TFs). Pituitary progenitors expressing Pit-1 are driven towards the somato-lacto-thyrotroph differentiation, T-Pit towards corticotroph, and SF-1 towards gonadotroph. We recently generated a multi-genomic classification of pituitary neuroendocrine tumors (PitNETs) (abstract submitted to ECE2019 by Neou M.). Transcriptome classification identified si...

The prolonged exposure to an excess of circulating cortisol (Cushing’s syndrome) causes various complications. An accurate and early diagnosis is critical for effective surgical management and optimal prognosis. However, the current diagnostic approach based on hormonal assays can be complex and requires multiple tests. The identification of novel, specific and easily measurable biomarkers of hypercortisolism may help to improve the diagnosis and to evaluate the complicat...

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...

The cortisol secretion level of adrenocortical adenomas range from hormonally silent to overt hypercortisolism. The mechanisms leading to the autonomous hypersecretion of cortisol are unknown. The aim was to identify the gene expression alterations associated with the autonomous and excessive cortisol secretion of adrenocortical adenomas.Methods: The transcriptome of 22 unilateral adrenocortical adenomas (5 non-secreting, 6 subclinical cortisol-producing...

Diagnosing malignancy and assessing the prognosis of adrenocortical tumors is challenging. The aim is to identify molecular predictors of malignancy and of survival.Patients and methods: Of 153 unilateral adrenocortical tumors were studied by microarray (n=92) or RT-qPCR (n=148). A 2-gene predictor of malignancy was built using the disease-free survival as the end-point in a training cohort (n=47), then validated in an independent va...

Adrenocortical tumor (ACT) is a rare, heterogeneous malignancy whose pathogenesis is unclear. The oncoprotein PTHrP, found in many common tumors, can regulate their growth in an autocrine/paracrine fashion through the receptor PTH-R1. Little is known about the role of PTHrP in ACT. We monitored the synthesis of PTHrP and PTH-R1 in a series of 25 ACT: 12 adrenocortical carcinoma (ACC), 13 adrenocortical adenoma (ACA), and investigated the effects of PTHrP (1–34) on H295R c...

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 (...

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...