Endocrine Abstracts

Recently, we provided the first integrated genomic classification of pituitary neuroendocrine tumors (PitNETs), on a series of 134 tumors. This series covered all histological, secretion, invasion and growth speed types. This molecular classification supports the importance of pituitary lineage as proposed by the World Health Organization 2017 classification, but also individualizes new entities. Indeed, corticotroph tumors are split into three distinct molecular groups. In ad...

Objective: We have described constitutional duplications of the PRKACA gene locus (encoding the catalytic subunit of the Protein Kinase A) in rare cases of bilateral nodular adrenocortical cause of Cushing’s (Beuschlein et al, NEJM 2014). Its frequency in macronodular and micronodular adrenal diseases and the occurrence of others manifestation of Carney complex are not clearly established. This study performs its systematic screening in a large cohort of adrenoco...

Objective: Carney Complex (CNC) is a rare hereditary genetic syndrome, mostly due to inactivating pathogenic variants of the tumor suppressor gene PRKAR1A. It has a wide spectrum of manifestations with frequent pigmented skin lesions, cardiac myxomas, primary pigmented nodular adrenocortical dysplasia, acromegaly and thyroid cancers. Breast benign tumors (fibroadenomas, ductal adenomas and myxoid lesions) have been associated with CNC, but so far, association with mal...

Introduction: Bilateral macronodular adrenocortical disease (BMAD) is an adrenal cause of Cushing’s syndrome explained in a subset of patients by inactivation of the tumor suppressor genes ARMC5 or KDM1A. Genetic and transcriptomic studies cluster BMAD in 3 distinct molecular groups: one with ARMC5 inactivation, one with KDM1A inactivation and a third group with no known genetic cause. Although ARMC5 and KDM1A are invo...

The most frequent molecular alteration in adrenocortical tumors (ACT) is the activation of the Wnt/β-catenin pathway that is associated with poor prognosis in adrenocortical carcinoma. Activating β-catenin mutation (p.S31, p.S37, p.S45, T.41) inhibiting its proteosomal degradation by the canonical destruction complex is responsible for its abnormal activation in roughly 30% of ACT. However, the E3 ubiquitin protein ligase 1, SIAH1 is able to ubiquitinate β-caten...

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...

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...

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 (...