Endocrine Abstracts

Context: Primary aldosteronism (PA) is the most common cause of secondary hypertension. Aldosterone excess can cause oxidative stress and respectively DNA damage in vitro and in vivo and increased levels of oxidative stress have been demonstrated in PA patients. Single case reports describe a coincidence of PA with renal cell carcinoma (RCC) and other tumours. However, so far no data on the prevalence of benign and malignant neoplasms in patients with PA exis...

Background: The water deprivation test as the accepted gold standard in the differential diagnosis of polyuria polydipsia syndrome can be associated with a decrease in extracellular fluid volume in patients with diabetes insipidus (DI). We herein evaluated mid-regional pro-atrial natriuretic peptide (MR-proANP) as marker of extracellular body volume in patients with diabetes insipidus compared to primary polydipsia (PP), at baseline and after water deprivation.<p class="ab...

Introduction: Adrenocortical tumours comprise frequent adenomas (ACA) and rare highly malignant carcinoma (ACC). Livin/ML-IAP/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumorigenesis, mostly through the inhibition of caspase-3. Aim of the study was to evaluate the expression of livin/BIRC7 in normal and neoplastic adrenal glands.Methods: The mRNA expression of BIRC7, its isoforms livin α...

Introduction: The correct differential diagnosis of the disorders related to polyuria–polydipsia syndrome (PPS) is mandatory since inadequate treatment may lead to serious complications. The diagnostic gold standard is the water deprivation test (WDT) with direct or indirect measurement of plasma vasopressin (AVP). But test interpretation is problematic, and direct measurement of AVP is hampered by methodological difficulties. The aim of this study was to evaluate the dia...

Background: Mitotane is the only drug approved for treatment of adrenocortical carcinoma (ACC). Molecular events leading to cell death in adrenocortical cells are unknown preventing the development of drugs with improved efficacy-toxicity ratio.Methods: We employed the ACC model cell line NCI-H295 to investigate the effects of mitotane on genome-wide mRNA expression using microarray analysis. Several algorithms were used to delineate signaling pathways t...

Purpose: Mitotane is the reference systemic therapy for adrenocortical carcinoma (ACC), but its mechanism of action and possible predictors of treatment response remain poorly defined. Our aim was to evaluate the gene expression of ribonucleotide reductase large subunit 1 (RRM1) and excision repair cross-complementation group 1 (ERCC1) in ACC as potential biomarkers for clinical outcome and response to mitotane.Experimental design: Forty-five and 47 tiss...

We have demonstrated that adjuvant mitotane prolong recurrence free survival (RFS) in patients with radically resected ACC. Aim of the present study was to correlate mitotane levels with patient outcome in an adjuvant setting in 3 different referral centres in Europe. There were 120 patients (45 W, 75 M, median age 44 years, range 16–76) radically resected for ACC who were treated adjuvantly with mitotane from 1996 to 2010. ACC was stage I in 10 cases, II in 73, III in 31...

Radiation therapy is a useful adjuvant tool for the management of difficult acromegalic patients. Its effects on cardiovascular morbidity are still unknown. Aim of the study was to investigate the long-term effects of radiotherapy on metabolic parameters and cardiovascular risk factors.A total of 42 acromegalic patients (11 M and 31 F, age: 55±12 years, RT group), cured after conventional RT (CRT, n=31) or radiosurgery by gamma-knife (GKRS, <...

Background: The multi-tyrosine kinase inhibitor sunitinib is approved for advanced renal cell carcinoma and gastrointestinal stroma tumors. It targets both tumor vessels and malignant cells. Animal experiments have pointed to a direct adrenotoxic effect of the drug.Aims: We hypothesized that sunitinib may inhibit proliferation of adrenocortical cancer (ACC) cells and influence adrenal steroid hormone synthesis.Results: Sunitinib re...

Introduction: Glucocorticoids (GC) are used for immunosuppression in many clinical conditions. Pre-clinical and early clinical studies suggested that the induction of regulatory T (Treg) cells contributes to the immunosupressive effects of GCs. However, in the hitherto reported clinical studies only patients with ongoing autoimmune diseases were included. Our goal, therefore, was to determine the influence of exogenous GCs in vivo in immunocompetent subjects and mice.</...