Endocrine Abstracts

Background: Adrenocortical carcinoma is a rare endocrine malignancy with poor prognosis and few treatment options in advanced disease. Immune checkpoint inhibitors (ICI) have been studied in few clinical trials with a limited number of patients in ACC. No real-life data are available so far. In the present study we aimed at evaluating treatment response and safety of ICI treatment in advanced ACC and identifying clinical, biochemical, histological and molecular markers for pre...

Adrenocortical carcinoma (ACC) is a rare malignancy with limited treatment options and a heterogenous prognosis. The histological diagnosis of ACC is complex and there is increasing interest in identifying and validating new immunohistochemical markers. Delta-like non-canonical Notch ligand 1 (DLK1) is a cleavable single-pass transmembrane protein. In humans, DLK1 is present in many tissues during foetal development, is restricted to progenitor/stem cells in a few adult tissue...

Background: Adrenocortical cancer (ACC) is a rare malignant neoplasm with a dismal prognosis, particularly in advanced disease. For these patients only limited therapeutic options are available. Adavosertib (AZD1775) is a potent inhibitor of tyrosine kinase WEE1 that regulates cell cycle checkpoints, slowing cell cycle progression and leading to mitotic entry in the presence of DNA damage. Therefore, its use could potentiate existing DNA damage-based therapies. Here, we evalua...

Background: The differential diagnosis of diabetes insipidus is challenging. The most reliable diagnostic approach is hypertonic saline-stimulated copeptin measurements. However, as this test is based on the induction of hypernatremia, it is associated with adverse effects and needs close sodium monitoring. We hypothesized that arginine-stimulated copeptin measurements provide an alternative, simple and safe diagnostic test for diabetes insipidus.Methods...

Protein Kinase A (PKA) consists of two catalytic and two regulatory subunits with several isoforms (Cα,β,γ, RIα,IIα,Iβ,IIβ). In 30–40% of cortisol-producing adrenocortical adenomas (CPA) heterozygous activating somatic mutations in the catalytic subunit α (Cα) of PKA have been found. Previous reports found strikingly reduced levels of RIIβ in CPA compared to other adrenocortical tumors. Here, we investigated the correlatio...

Background: Adjuvant mitotane therapy is frequently used in Europe following surgery for adrenocortical carcinoma (ACC). Management of adjuvant mitotane is mainly empirical and a major open question is the optimal duration of therapy, because no study has ever addressed this issue.Objective: We aimed to assess the outcome of ACC patients who were treated with adjuvant mitotane for at least one year following surgery and then discontinued therapy for othe...

Adrenocortical carcinoma (ACC) is a rare tumor with poor prognosis and the only approved drug for advanced disease is mitotane. The cytochromes P450 (CYP) 2W1 and 2B6 are proposed predicting markers of sensitivity to mitotane treatment. Aim of the study was to evaluate the relationship between CYP2W1 and/or CYP2B6 polymorphisms and response to mitotane in ACC.Methods: We performed a multicentric retrospective study including 182 ACC patients (F/M=121/61)...

Introduction: Adrenocortical carcinoma (ACC) is an aggressive malignancy with a high rate of recurrence. Regular post-operative follow-up imaging is necessary, but associated with high radiation exposure and frequent diagnostic ambiguity. Urine steroid metabolomics has recently been introduced as a novel diagnostic tool for the detection of adrenocortical malignancy in patients with adrenal incidentalomas. Here we present the first clinical study assessing the performance of t...

Background: Genetic alterations underlying the pathogenesis of autonomous cortisol secretion and early adrenocortical tumorigenesis have been identified in 40% of adrenocortical tumors (ACT). Nonetheless, the molecular events leading to development of ACT and steroid secretion remain obscure for a large proportion of patients.Aim: Aims of our study were to investigate the relationship between transcriptome profile and genetic background in a large series...

Background: The human cytochrome P450 (CYP) 2W1 is involved in the metabolism of several endogenous substrates, including lysophospholipids and fatty acids. Using a polyclonal antibody, we previously demonstrated a high CYP2W1 immunoreactivity in adrenocortical tumors, particularly in those secreting steroids. The aim of the study was to better elucidate the relationship between CYP2W1 and steroid secretion in adrenocortical carcinoma (ACC) H295R cell line and in a larger seri...