Endocrine Abstracts

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...

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...

Introduction: Bilateral Macronodular Adrenocortical Disease (BMAD) is a rare cause of Cushing syndrome due to bilateral adrenocortical macronodules. Germline inactivating variants of the tumor suppressor gene ARMC5 have been described by our group 10 years ago and are responsible for 20-25% of apparently sporadic BMAD cases and 80% of familial presentations. ARMC5 patients present with a more pronounced phenotype than wild-type patients, in terms of cortisol ...

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: Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) is a rare disease responsible for variable levels of cortisol excess. Constitutional pathogenic variants of the tumor suppressor gene ARMC5 are its most frequent molecular cause (20% of index cases). Recently, KDM1A has been identified as the causing gene for PBMAH associated with food-dependent Cushing’s syndrome (FDCS), consecutive to the illegitimate expression of the GIP recepto...

Introduction: In Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH), cortisol secretion may be consecutive to physiological stimuli, through the illegitimate expression of G-protein coupled receptors (GPCR) in adrenocortical cells. The most characterized is the overexpression of GIP receptor (GIPR) leading to food-dependent Cushing syndrome (FDCS) but it has not been associated with the consecutive inactivation of ARMC5 responsible for 25% of PBMAH. This work aimed to ...

Background: Bulk genomic studies have identified distinct molecular classes 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 (“bulk&...