Endocrine Abstracts

The cAMP signaling pathway plays a major role in the pathogenesis of cortisol-producing adrenocortical adenomas (CPA). In adrenocortical cells cAMP induces dramatic changes in cell morphology accompanied by actin cytoskeleton rearrangements that precede steroidogenesis, the causal relationship between these events being still undefined. In this study we investigated cAMP effects on cytoskeleton rearrangements and steroidogenic response in mouse (Y1) and human adrenocortical tu...

Mitotane is the only approved drug for the treatment of advanced adrenocortical carcinoma (ACC) and we recently demonstrated that a high expression of cytochrome P450 2W1 (CYP2W1) correlated with response to mitotane. The association between CYP2W1 alleles and a generally increased cancer risk is under debate. Aim of the study was to evaluate the frequency of CYP2W1 polymorphisms and its correlation with the response to mitotane treatment in ACC patients.<p class="abstext"...

Recently, somatic, heterozygous mutations in the gene encoding the deubiquitinase USP8 have been identified in 30–60% of corticotroph tumors. These mutations were found to hinder binding of 14-3-3 proteins, increasing its deubiquitinating activity. One substrate is Epidermal Growth Factor Receptor (EGFR), USP8 triggering EGFR recycling and increased EGFR signaling. However, tumors harboring mutations in USP8 are smaller than WT tumors, raising the debate if EGFR, as a pot...

Background: Heterozygous activating somatic mutations in the catalytic subunit α (Cα) of Protein Kinase A (PKA) underlie 30–40% of cortisol producing adrenocortical adenomas (CPA). The activity of the catalytic subunits α,β,γ is controlled by the regulatory subunits (Iα,Iβ, IIα, IIβ). Previous reports found uncommonly reduced levels of RIIβ in CPA compared to other adrenocortical tumors.Aim: Investig...

Background: Adrenocortical carcinoma (ACC) has a heterogeneous prognosis and current medical therapies have limited efficacy in its advanced stages. Genome-wide multi-omics-studies identified molecular patterns associated with clinical outcome. Here, we aimed at identifying a molecular signature useful for both personalized prognostic stratification and druggable targets, using methods applicable in clinical routine.Methods: 117 tumor samples from 107 AC...

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...

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...

Adult GH deficiency syndrome is characterized by visceral obesity, dyslipidemia, insulin resistance and is associated with an increased cardiovascular risk. Epicardial adipose tissue, giving its relationship with abdominal visceral adiposity, coronary artery disease, cardiac morphology and function and metabolic syndrome, has been proposed as cardio-metabolic risk indicator. In this study, we evaluated the echocardiographic epicardial fat thickness in 14 patients (8 M and 6 F,...

Background: GH response to oral glucose tolerance test (OGTT) is currently used for the definition of disease remission in acromegaly. This test has been poorly investigated in other pituitary diseases.Aim: To evaluate the impact of a pituitary disease other than acromegaly on GH response to OGTT.Patients and methods: Eighteen patients (13 F & 5 M, age: 50.7±13.1 years) with different pituitary diseases (i.e. non-functioni...

A high risk for small bowel (SB) tumors in acromegalic population has been reported in a cohort study (Baris D, 2002). SB lesions may be easily investigated by the recently developed videocapsule endoscopy (VCE). Aim of the study was to assess the prevalence of SB neoplasms by VCE in 14 acromegalic patients (Ac) in respect to 30 sex and age-matched control subjects and to correlate it with cancer risk factors and acromegaly-related parameters. Local Ethical committee approved ...