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...

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: 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....

Background: Adrenocortical carcinoma (ACC) has an aggressive but heterogenous behaviour. ENSAT stage and Ki67 proliferation index are used to predict clinical outcome but are limited in distinguishing patients with best outcome. We aimed to validate the prognostic role of clinical and histopathological parameters alone or combined by applying a previously proposed points-based score (mGRAS, Lippert JCEM 2018) to a large multicentre cohort of ACC patients.<p class="abstext"...

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 ...

BackgroundThe ESE-ENSAT guidelines suggest adjuvant mitotane for patients with adrenocortical carcinoma (ACC) at high risk of recurrence following radical surgery. This indication has a limited evidence base, lacking results from randomized controlled trials. No suggestion is available in low-risk patients, since studies did not stratify patients for prognosis. The randomized controlled study ADIUVO compared the efficacy of adjuvant mitotane (MIT) treatm...