Endocrine Abstracts

Background: Increasing age is associated with poorer survival in DTC [Oyer SL, 2012]. In the phase 3 COSMIC-311 trial (NCT03690388), cabozantinib, an inhibitor of VEGFR2, MET, AXL and RET, significantly improved the progression-free survival (PFS) vs placebo in previously treated patients with RAI-R DTC (HR 0.22, 96% CI 0.13-0.36; P<0.0001; median follow-up 6.2 months). The impact of age on efficacy and safety was included in the prespecified subgroup analysis.</p...

Background: Central diabetes insipidus (cDI), a rare neuroendocrine condition affecting 1 in 25.000, is characterized by deficiency of arginine vasopressin. Data about treatment-related side effects, psychological co-morbidities, and incidence of wrong management due to confusion with diabetes mellitus are scarce and limited to small studies or case series. Furthermore, increasing interest has arisen on a potential need for re-naming the condition.<p class="abstex...

Background: New therapeutics and combinations are needed to improve the survival of patients with advanced, metastatic pancreatic NETs (pNETs). RABL6A is a novel oncogenic driver of pNET pathogenesis that acts through multiple oncogenic pathways. Kinome and phosphoproteome analyses of proliferating (RABL6A-positive) pNET cells, vs arrested (RABL6A-knockdown) controls, demonstrated that druggable cyclin-dependent kinase 4 and 6 (CDK4/6) and MEK kinases are activated in growing ...

Clinical features of the primary prostate tumor remain insufficient for clinicians to accurately define patients at highest risk of developing metastases. However, the primary tumor is the source of these metastases, and thus should contain information on its metastatic potential. We hypothesized that the combination of a primary tumor’s copy number alterations (CNAs) and genome-wide transcriptome information would give us more insight in the biology of metastases-prone l...

Background: Patients with long-term remission of Cushing’s disease (CD) demonstrate residual psychological complaints. At present, it is not known how previous exposure to hypercortisolism affects psychological functioning in the long-term. In foregoing Magnetic Resonance Imaging (MRI) studies, abnormalities of brain structure and resting-state connectivity were demonstrated in patients with long-term remission of CD. However, no data are available on functional alteratio...

The mTOR and IGF pathways have been suggested to play a role in the pathogenesis of pheochromocytomas (PCC). mTOR inhibitors, as sirolimus (S) and everolimus (E), as well as IGF1R antagonists could be a potential novel treatment for malignant PPC.The aim of this study was to evaluate the expression of the main components of the IGF/mTOR pathway in human PCC and to investigate the effects of the mTOR inhibitors S and E and of the IGF1R/insulin receptor (I...

Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder characterized by lifelong elevation of serum calcium concentrations with inappropriately low urinary calcium excretion. Three types referred to as FHH1, FHH2 and FHH3 and located on chromosomes 3q21.1, 19p and 19q13.3, respectively, have been reported. FHH1, caused by loss-of-function mutations of the calcium-sensing receptor (CaSR), accounts for >65% of FHH patients. To identify the gen...

The European Registry on Cushing’s syndrome (ERCUSYN) is designed to collect prospective and follow-up data at EU level on patients with Cushing’s syndrome (CS). Baseline data on 481 CS patients (390 females, 91 males; mean age (±S.D.): 44±14 years) collected from 36 centres in 23 countries. This cohort included new patients since 2008 and retrospective cases since 2005. Patients were divided into four major etiologic groups: pituitary-depend...

Background: Adrenocortical carcinoma (ACC) is an uncommon malignancy with a still scantily understood pathogenesis and generally poor prognosis. Many patients with ACC need new treatment options. mTOR inhibitors, as sirolimus (S) and temsirolimus (T), are promising antineoplastic drugs in several kinds of tumors.Methods: In three human ACC cell lines (H295, HAC15 and SW13), we evaluated the mTOR and IGF2 expression at mRNA level (by qPCR) and at protein ...

Chronic exposure to hypercortisolism has a significant impact on patient’s health and Health-Related Quality of Life (HRQoL), as demonstrated with generic questionnaires. Objective: Develop and validate a disease-generated questionnaire to evaluate HRQoL in patients with Cushing’s syndrome-CS- (Cushing QoL). Methods: After a literature review, interviews with expert endocrinologists and 10 patients identified HRQoL domains and clinical aspects of the disease; an anal...