Endocrine Abstracts

Pathogenic ARMC5 variants are the main genetic cause of Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) explaining roughly 20% of index cases. These variants found both at germline and somatic level are mostly frameshift and nonsense leading to a loss of its function. ARMC5 acts then, as a tumor suppressor gene but little was initially known on its function. Using an RNAseq analysis on transient zebrafish models of Armc5 up- and d...

Objective: To describe the Carney Complex (CNC) manifestations presented by patients harboring the PRKAR1A mutation c.709(-7-2)del (one of the three hotspots) in a large cohort of patients.Methods: Multicenter retrospective study. Age at the diagnosis or at the screening of the different CNC manifestations is described by mean ± standard deviation.Results: Forty patients [12 index cases, 27 females, 46±15 years o...

Introduction: Sirolimus, a mTOR (mechanistic Target of Rapamycin) inhibitor, is well known for its impact on glucides and lipids metabolism. These effects vary according to factors such as dose and treatment duration, species, cell types and environmental factors. In vitro and in vivo, sirolimus inhibits adipogenesis by decreasing adipocytes number and size, as well as pre-adipocytes differentiation, leading to subcutaneous and visceral fat mass decrease in m...

Introduction: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare aetiology of Cushing syndrome. Familial clustering suggests a genetic cause that was recently confirmed, after identification of inactivating germline mutations in armadillo repeat containing 5 (ARMC5) gene.Clinical case: A 70 years old female admitted due to femoral neck fracture in May 2014, presented central obesity, rubeosis and hypertension. Laboratory work up reveale...

Background: Lamin A/C mutations show heterogeneous phenotypes expanding from cardiopathies to lipodystrophies. R482-LMNA gene mutation is the hot-spot for familial partial lipodystrophic syndromes (FPLD2) and is characterized by an increase of intra-abdominal (visceral) fat. In contrast, the visceral fat phenotype of non-R482-LMNA mutated patients has not been well studied.Objectives: To compare the fat amount and visceral repartition o...

ARMC5 is a tumor suppressor gene responsible for 20 to 40% of Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) with a function that remains unclear. Based on pathway analysis from RNAseq results obtained on zebrafish models of transient Armc5 up- and down-regulation, we identified transcriptional alterations of several members of SIRT1 (sirtuin (silent mating type information regulation 2 homolog) 1) signaling in our models and hypothesized that ARM...

Introduction: Germline inactivating ARMC5 (Armadillo repeat containing 5) mutations are responsible for Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH). ARMC5 presents the characteristics of a tumor suppressor gene. Mutations are observed in more than 85% of patients with a clear familial presentation and 20 to 25% of apparently sporadic cases. Genetic alterations are spread all over ARMC5 coding sequence and more than two-third of them ar...

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...

Background and purpose: Type 1 myotonic dystrophy (MD), associates neuromuscular, cardiac, respiratory and endocrine disorders. The aim of this study was to determine the prevalence of thyroid disorders and of any causal factors.Methods: A retrospective single centre study was conducted, between 2000 and 2016, in 127 MD patients, diagnosed by familial genetic screening after informed consent. Clinical examination, TSH assay, 120-min glucose and insulin l...

Introduction: ARMC5 germline and somatic inactivating mutations were discovered in patients treated by adrenalectomy for hypercortisolism due to primary bilateral macronodular adrenal hyperplasia (PBMAH). Since then, several ARMC5 germline variants have been described in PBMAH patients. Genetic alterations are spread all over ARMC5 coding sequence and many are missense variants. For them, geneticist conclusions are based on in silico predictions. As ...