Endocrine Abstracts

Introduction: Steroid profiling by mass spectrometry approaches consists in the simultaneous measurement of several steroid molecules in a biological sample, allowing an optimal characterization of steroidogenesis alterations, particularly in the context of adrenal tumors. Twenty-four hours urine samples have the advantage of being non-invasive and of giving an integrated view of steroidogenesis. Urinary steroid profiling has thus been shown to be particularly useful in the di...

Some elegant clinical observations of dysregulated cortisol-secretion in cases of ACTH-independent macronodular hyperplasia (AIMAH) and more rarely adrenocortical adenomas (ACA) have led to the concept of ‘aberrant’ or ‘illegitimate’ membrane receptors (AR) in adrenal Cushing syndrome. It this situation cortisol secretion is regulated by an extra-cellular ligand that usually does not stimulate cortisol secretion in normal adrenals. This abnormal response mi...

Introduction: Alterations of the cAMP signaling pathway are described in adrenal tumors causing Cushing syndrome, specifically mutations in the gene coding for the protein kinase A (PKA) catalytic subunit alpha (PRAKCA) in cortisol producing adenomas (CPA) with overt Cushing syndrome.Materiel and Methods: Eight CPAs without PRKACA mutations were analyzed by whole exome sequencing. Direct sequencing of PRAKCB encoding for the catalytic subunit beta (C&#94...

Introduction: Adrenocortical Carcinoma (ACC) is a rare and aggressive tumor with poor prognosis. Up to now, CTNNB1 (βcatenin) and TP53 mutations were the most frequent alterations identified in ACC. By a combination of genomic approaches, we have recently analyzed a cohort of 122 ACC (European Network for the Study of Adrenal Tumors, ENSAT). This work confirmed recurrent alterations in CTNNB1 and TP53 and revealed new genes not previous...

The outcome of ACTs can be determined by gene expression level at the RNA level. However RNA handling is challenging. In contrast tumor DNA is robust and therefore easier to use.Aim: To characterize the ACTs DNA alterations; to identify markers with diagnostic and prognostic value using tumor DNA.Methods: The mapping of chromosomal gains and losses of 60 ACTs (39 adenomas (ACAs), 21 carcinomas (ACCs)) was performed with CGH arrays ...

Introduction: Osilodrostat is a new 11 ß-hydroxylase inhibitor with a mode of action analogue to metyrapone. It has become increasingly used in recent years for treatment of Cushing’s Syndrome (CS). However, few in vivo studies are currently available to accurately compare both drugs characteristics. The objective of our study was to compare steroidogenic profiles in patients treated by either Osilodrostat or Metyrapone for ACTH-dependent CS.Me...

Background: Cushing’s syndrome, caused by an excess of circulating glucocorticoids, is associated with high morbidity and presents high inter-individual variability. The earlier the diagnosis, the better the treatment effectiveness and the prognosis. Hormone assays, routinely used, contribute to identify Cushing’s syndrome. However, no biomarker is currently available to directly quantify the biological action of glucocorticoids. Blood samples represent an easily obt...

Introduction: Biological diagnosis of Cushing syndrome relies on three parameters: 24 hours-free urinary cortisol; serum cortisol after 1 mg dexamethasone suppression test; late-night serum or salivary cortisol. These tests allow the diagnosis of cortisol excess but do not help in etiological diagnosis, particularly in the distinction between pseudo-Cushing and ACTH-dependent Cushing syndrome, which is often challenging. The aim of this study was to evaluate the performances o...

Rationale and aim: A recent pangenomic study documented a subset of somatotroph mostly GNAS-wildtype PitNET/adenomas co-express steroidogenic factor 1 (SF1). Aim of our study was to investigate clinical and molecular features of a cohort of these tumour subtype. Study sample: We identified 20 cases of SF1-expressing somatotropinomas out of 173 (11.6%) operated via transsphenoidal endoscopic approach in 3 referral Pituitary Centers patients. Pre- and post...

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...