Endocrine Abstracts

Background: Germline mutations of ARMC5 (Armadillo repeat containing 5 gene) were identified as a frequent cause of primary bilateral macronodular adrenal hyperplasia (PBMAH). ARMC5 is considered as a tumor suppressor gene regulating apoptosis and steroidogenesis by unknown mechanisms. The ARMC5 protein contains a N-terminal domain made of Armadillo (ARM) repeats and a C-terminal ‘Bric-a-Brac, Tramtrack, Broad-complex/Pox virus and Zinc finger (BTB/POZ)&...

Background: The mechanisms causing hypercortisolism in primary macronodular adrenocortical hyperplasia (PMAH) are not fully clarified. The participation of ectopic receptors and autocrine/paracrine regulation of intra-adrenal ACTH in hyperplastic tissue have been considered. Additionally, germline ARMC5 mutations have been described as main cause of PMAH. So far, the functional study that analyzed the role of ARMC5 used the adrenocortical carcinoma cell line, H295R. T...

Background: ARMC5 (armadillo repeat containing 5) has been identified as the gene responsible for PBMAH (Primary Bilateral Macronodular Adrenal Hyperplasia). ARMC5 inactivating mutations are reported in 20 to 25% of PBMAH patients. ARMC5, is considered as a tumor suppressor gene controlling apoptosis and regulating steroidogenesis. The mechanisms of action of ARMC5 are unknown. The structure of the ARMC5 protein contains ARM repeats and a BT...

Adrenocortical Carcinoma (ACC) is a rare and lethal disease with a poor prognosis. This study aims to share our 41-year experience as a referral center, focusing on identifying risk factors associated with ACC mortality. Our retrospective analysis included a cohort of 150 adult patients with ACC in all stage categories, treated between 1981 and 2022. Tumor hormonal hypersecretion was observed in 78.6% of the patients, and the median age of diagnosis was 40 years. The majority ...

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...

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis. Despite the poor prognosis in the majority of patients, no improvements in treatment strategies have been achieved. Therefore, the discovery of new prognostic biomarkers is of enormous interest. Sterol-O-acyl transferase 1 (SOAT1) is involved in cholesterol esterification and lipid droplet formation. Recently, it was demonstrated that SOAT1 inhibition leads to impaired steroidogenesis ...

Introduction: Masses in adrenal topography have been diagnosed frequently due to more available access to radiological imaging. Adrenal incidentalomas occur around 5% to 7% of patients undergoing abdominal imaging mainly over 50 years of age. The HCFMUSP is a complex tertiary center, a national reference to adrenal disorders and since 2006 around 300 adrenalectomies were performed; 8% of them corresponded to undetermined masses in adrenal topography.Obje...

Objective: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is the most common cause of Cushing’s syndrome with bilateral adrenal origin. Pathogenic variants of ARMC5 and KDM1A tumor suppressor genes are causing around 25% of isolated PBMAH cases and variants of PDE11A gene, are frequently associated with the disease, but causality has not been formally established. Methods: The leukocyte DNA of 354 index cases of PBMAH, from 8 European, A...

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 ...

Recent studies have reported a high prevalence of USP8 mutations in corticotroph adenomas causing Cushing’s disease. Nelson’s syndrome is a potentially life-threatening complication of bilateral adrenalectomy in patients with refractory Cushing’s disease that is caused by the development of an ACTH-secreting tumor in the pituitary gland. Whether USP8 alterations are also present in Nelson’s tumors has not been studied in detail so far....