Endocrine Abstracts

Pituitary adenomas, now called pituitary neuroendocrine tumors (PitNETs), vary in histological type, secretion, invasion and growth speed. A World Health Organization (WHO) histo-prognostic classification was released in 2017. Pituitary tumorigenesis is largely unexplained. Rare germline mutations (MENIN, AIP), and common somatic mutations in somatotroph (GNAS) and corticotroph (USP8) are reported. Recently, genomic analyses have been report...

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...

In the human adrenal gland, serotonin (5-HT), released by subcapsular mast cells stimulates corticosteroid secretion through activation of type 4 serotonin receptors (5-HT4R) positively coupled to cAMP/proteine kinase A (PKA) signaling pathway and calcium influx. The 5-HT4R is principally expressed in zona glomerulosa cells explaining why 5-HT strongly stimulates aldosterone production but only exerts a modest stimulatory action on cortisol. Interestingly, in primary pigmented...

Introduction: The French National Institute of Cancer (INCa) launched supported by the Ministry of Health in 2008 a program for the recognition of national networks for the management of rare cancers. Among the 23 selected networks COMETE-Cancer was recognized by INCa in 2009 for Adrenocortical carcinoma (ACC) and malignant pheochromocytoma/paraganglioma (MPP). At that time 60–120 new ACC/year and 30 new MPP/year were expected at the national level....

In human adrenals, serotonin (5-HT), released by subcapsular mast cells, increases aldosterone secretion through activation of type 4 serotonin receptors (5-HT4R) but only exerts a modest control on cortisol production. Interestingly, illicit synthesis of 5-HT in adrenocortical cells as well as overexpression of the 5-HT4R and ectopic expression of the type 7 receptor (5-HT7R) have been observed in bilateral macronodular adrenal hyperplasia res...

The cAMP signaling pathway plays a major role in the pathogenesis of cortisol-producing adrenocortical adenomas (CPA). In adrenocortical cells cAMP induces dramatic changes in cell morphology accompanied by actin cytoskeleton rearrangements that precede steroidogenesis, the causal relationship between these events being still undefined. In this study we investigated cAMP effects on cytoskeleton rearrangements and steroidogenic response in mouse (Y1) and human adrenocortical tu...

Background: Heterozygous activating somatic mutations in the catalytic subunit α (Cα) of Protein Kinase A (PKA) underlie 30–40% of cortisol producing adrenocortical adenomas (CPA). The activity of the catalytic subunits α,β,γ is controlled by the regulatory subunits (Iα,Iβ, IIα, IIβ). Previous reports found uncommonly reduced levels of RIIβ in CPA compared to other adrenocortical tumors.Aim: Investig...

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...