Endocrine Abstracts

Introduction: Patients with Parkinson’s disease on pharmacological treatment frequently loose weight but regain weight after subthalamic nucleus deep brain stimulation (SNBS). This is, at least in part, due to an increase in resting energy expenditure (Perlemoine et al., Br J Nutrition 2005; 93). As SNBS electrodes are located close to the hypothalamic centre regulating food intake, we investigated whether ghrelin levels would vary with SNBS and/or L-DOPA tr...

Introduction: Osilodrostat and Metyrapone are two CYP11B1 inhibitors used for the treatment of patients with Cushing syndrome. Despite their common suspected mechanism of action, the comparison of serum steroid profiles determined in HPLC-MS/MS in patients treated by either Osilodrostat or Metyrapone for an ACTH-dependent Cushing syndrome identified higher levels of 11-deoxycortisol and androgens in patients treated by Metyrapone than in those treated by Osilodrostat (F. B...

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...

Mitogen-activated protein kinase (MAPK) pathway abnormalities, specifically rearrangements (RET/PTC) or activating mutations (RAS or BRAF), are highly prevalent in papillary thyroid carcinomas (PTCs). Constitutive activation of this signaling cascade causes sustained phosphorylation of extracellular signal-regulated kinase (ERK). DUSP5, which is positively regulated by ERK signaling, acts as a negative regulator of its activity. We have previously shown that DUSP5 is overexpre...

The cAMP signaling pathway plays an important role in cell proliferation and differentiation, and can be altered at multiple levels in endocrine tumors. Its central component is the protein kinase A (PKA). Inactivating mutations of PRKAR1A are observed in CNC (a dominant autosomal hereditary disease responsible for primary pigmented nodular adrenocortical disease, cardiac myxoma and lentiginosis). Most PRKAR1A mutations lead to mRNA unstability and protein degrad...

cAMP/PKA pathway activation is frequently involved in endocrine tumors with overactivity. The Carney complex (CNC) is an autosomal dominant multiple endocrine neoplasia syndrome which associates cardiac myxomas, spotty skin pigmentation and endocrine overactivity. Mutations in the PRKAR1A gene located at 17q22-24 and encoding for the R1A regulatory subunit of protein kinase A have been found in about 60% of CNC. These mutations are heterozygous germline mutations leading to ab...

BackgroundARMC5 is a putative tumor suppressor gene that is frequently mutated in primary bilateral macronodular adrenal hyperplasia (PBMAH), a rare cause of Cushing’s syndrome. The function of ARMC5 is poorly known, aside the fact that it regulates cell apoptosis and adrenal steroidogenesis in by mechanisms still unknown. Tumor suppressor genes play an important role in oxidative stress.MethodsIn this s...

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...

ACTH-independent macronodular hyperplasia (AIMAH) affects both adrenals, and familial forms are reported, suggesting a genetic origin. Rare mutations have been reported in several genes, including Gs alpha (GNAS), Phosphodiesterase 11A (PDE11A), Fumarate Hydratase (FH), and the Glucocorticoids receptor (GR).Objective: To assess the prevalence known genes mutations, and identify new candidate genes in AIMAH.Design and methods: Germl...

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 ...