Endocrine Abstracts

Adrenocortical carcinoma (ACC) is a malignant tumor with poor prognosis and no established therapy in advanced stage. Cisplatin is the most frequently used cytotoxic drug, but even combined with doxorubicin and etoposid, the response rate is <50%. Recently, it has been demonstrated that the excision repair cross complementing group 1 (ERCC1) plays a relevant role in the DNA repairing process, particularly in the correction of platinum-induced DNA adducts. Accordingly, ERCC...

Aim of this study was to evaluate the impact of rhGH treatment on glucose and lipid metabolism in in 26 patients (17M and 9F, age 47.0±11.1 years) with adult onset GH deficiency. Metabolic parameters (fasting glucose and insulin, glycated haemoglobin, lipid profile, body composition, OGTT) and indices of insulin resistance (IR) and sensitivity (IS), i.e. homeostasis model assessment (HOMA-IR and derived ISI-HOMA), quantitative insulin check index (QUICKI), ISI-composite, ...

Long-term effects of trans-naso-sphenoidal surgery (TNS) and long-acting somatostatin analogs (SSTa) on hypotalamic-pituitary-adrenal (HPA) function have been poorly investigated. Aim of the study was to evaluate over time the integrity of HPA axis in acromegalic patients with baseline preserved adrenal function and treated with one or both available treatments. We selected 23 patients (15F & 8M, age (±S.D.)=46.8±13.7 yrs) with normal (n=19)...

Protein Kinase A (PKA) consists of two catalytic and two regulatory subunits with several isoforms (Cα, β, γ and RIα, IIα, Iβ, IIβ, respectively). Type II regulatory subunits are phosphorylated by PKA in their inhibitory sites, while type I are not. Somatic activating mutations in the gene encoding the catalytic subunit α (Cα) of PKA (PRKACA) have been found in 30–40% of cortisol-producing adrenocortical adenomas (CPA). We rece...

We previously identified mutations in PRKACA, coding for the catalytic a (Ca) subunit of protein kinase A (PKA), as the main genetic alteration in cortisol-producing adrenal adenomas (CPAs) responsible for Cushing’s syndrome. Here, we further investigated the mechanism of action of all PRKACA mutations identified so far by our team (L206R, L199_C200_insW, S213R_L212_K214insIILR, C200_GlyinsV, W197R, del244-248+E249Q and E32V). Five out of seven mutants s...

Previously, we identified seven mutations in the main catalytic subunit of protein kinase A (PKA Cα) to be responsible for cortisol-secreting adrenocortical adenomas (CPAs): L206R, L199_C200_insW, S213R_L212_K214insIILR, C200_GlyinsV, W197R, del244-248+E249Q, E32V. Here we performed a functional characterization of these mutants. Specifically, we evaluated the association between PKA regulatory and catalytic subunits using co-immunoprecipitation and PKA activity using a k...

Adrenocortical carcinoma (ACC) is a rare tumor with heterogeneous outcome and no available targeted therapy. The aim of the study is to identify prognostic molecular markers and novel potential drug targets.A total of 43 FFPE tumor samples were retrospectively investigated for somatic mutations and copy number variations (CNV) by next-generation sequencing (160 cancer-related genes, Qiagen). Gene expression was evaluated by quantitative RT-PCR in a subgr...

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"...

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...