Endocrine Abstracts

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...

Introduction: Bilateral macronodular adrenal disease (BMAD) is a genetically heterogeneous disease that can be caused by ARMC5 or KDM1A alterations. Indeed, a germline and somatic event leading to a bi-allelic inactivation of ARMC5 or KDM1A are responsible for 20 and 1% of BMAD cases, respectively. Genetic analysis identified three molecular groups: ARMC5, KDM1A and no genetic cause known to date. Although there is a high h...

Introduction: PBMAH is an heterogeneous disease from the clinical, hormonal, and morphological point of view. ARMC5 inactivating mutations have been reported as a cause of PBMAH. PDE11A4 variants have been associated with PBMAH and NR3C1 variants with bilateral adrenal incidentalomas.Aim: To analyse the frequency of ARMC5 pathogenic mutations and PDE11A4 and NR3C1 variants in PBMAH patients.<p cla...

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: Carney Complex (CNC) is a rare genetic syndrome, with multiple endocrine and non-endocrine neoplasia, mostly due to inactivating mutations of the PRKAR1A gene. CNC has a wide spectrum of manifestations : most frequently skin lesions, cardiac myxomas and primary pigmented nodular adrenocortical dysplasia (PPNAD), but also thyroid nodules, schwannomas, breast tumors (mainly myxoid fibroadenomas and ductal adenomas)… The present study was designed to ...

IntroductionPrimary bilateral macronodular adrenal hyperplasia (PBMAH), the most common cause of adrenal Cushing’s syndrome due to bilateral adrenal tumors, is an heterogenous disease with various clinical, hormonal and morphological characteristics. ARMC5 inactivating mutations is the most frequent genetic cause of PBMAH and variants of PDE11A4 have been associated with the disease. In order to better understand the heterogeneity ...

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...