Endocrine Abstracts

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.</...

Introduction: O,p’DDD is the drug of choice for patients with adrenocortical carcinoma (ACC). Monitoring o,p’DDD serum level has been proposed as predictor of tumour response. Measurement of o,p’DDD metabolites involved in the active pathway may provide an improved prediction of o,p’DDD activity. The objective of our study was to (1)to confirm the currently used threshold o,p’DDD serum level of 14mg/l for achieving a tumour response and (2)compare the ...

Objectives: Endocrine gland-derived vascular endothelial growth factor (EG-VEGF; also termed prokineticin-1) has been identified as a mitogen preferable for the endothelium of steroidogenic glands (1). EG-VEGF and its receptors (prokineticin receptors 1 and 2; PKR1 and 2) are highly expressed in the normal adrenal gland and an autocrine mitogenic loop has been proposed (2). Therefore, we investigated the expression of EG-VEGF and its receptors in adrenocortical carcinoma (ACC)...

Introduction: The role of surgery for recurrent ACC is not well defined. Therefore, we used the German ACC Registry to evaluate treatment modalities after first recurrence in patients amenable to surgery.Methods: Patients with recurrence after radical resection and follow-up data were included. Patients with extensive metastasized disease (>2 tumoral organs, peritoneal carcinomatosis) were excluded. Progression-free and overall survival (PFS/OS) were...

Subject: Adrenal tumours (AT) are often detected incidentally and represent a variety of differential diagnoses with variable therapeutic consequences. We have recently developed [123I]Iodometomidate ([123I]IMTO), that specifically binds to adrenal CYP11B enzymes as a SPECT tracer for adrenal scintigraphy. This radiotracer is now evaluated in patients with adrenal tumours in an ongoing clinical trial. The study was approved by the ethical committee and pa...

Objectives: Adrenocortical carcinoma (ACC) is a rare malignancy with incompletely understood pathogenesis and poor prognosis. Overexpression of epidermal growth factor receptor (EGFR) has been demonstrated in several tumors and is partly associated with a more aggressive phenotype and a worse prognosis. In addition, targeting the EGFR tyrosine kinase represents a successful new therapeutic strategy, e.g. in non-small cell lung cancer. Therefore, we investigated the role of EGF...