Endocrine Abstracts

Introduction: Bilateral macronodular adrenal disease (BMAD, former PBMAH) is a rare cause of Cushing’s syndrome. The few morphologic descriptions of BMAD mention multinodular hyperplastic adrenal glands composed of clear spongiocytic cells and fewer compact eosinophilic cells without any morphologic variation. The discovery of ARMC5 and KDM1A mutations argues for genetic heterogeneity. The aim of this work was to describe the morphological and immunohist...

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: Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) is a rare cause of ACTH-independent Cushing syndrome. It is characterized by the development of supracentimetric nodules resulting in increased adrenal volume and weight. Its presentation is clinically, radiologically and biologically heterogeneous. Morphological descriptions of PBMAH are rare. Although the initial description highlights that multinodular hyperplastic adrenal glands are made of a majority...

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...

Background: Molecular classification is important for diagnosis and prognosis 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 (“bul...

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...