Endocrine Abstracts

Objective: Patients with adrenal insufficiency (AI) have been found to have increased cardiovascular morbidity, partly associated with nonphysiologic glucocorticoid replacement.Design: We included two separate cohorts (cohort 1 and 2) of patients with chronic primary and secondary AI under standard replacement therapy and compared them to two age- and sex-matched population-based studies (SHIP-TREND/DEGS). Patient cohort 1 comprised 389 individuals asses...

# These authors contributed equallyIntroduction: Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy with poor prognosis and limited treatment options. In addition, ACC is characterized by endogenous glucocorticoid (GC) excess in 60% of cases which is hypothesized to be one reason, why first clinical trials evaluating the potency of immune checkpoint blockade showed only modest results. Here, we report the identificati...

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy with poor prognosis and very limited treatment options in advanced disease. The only curative approach is complete surgical resection. Additionally, 60% of patients show endogenous glucocorticoid (GC) excess with clinical apparent hypercortisolism and low to no immune cell infiltration. To date, no therapeutically relevant surface markers are known for ACC, which is why it has not been con...

Sphingosine kinase 1 (SphK1) is the enzyme deputed to the phosphorylation of sphingosine in sphingosine-1-phosphate (S1P). S1P promotes ERK phosphorylation with increasing cellular proliferation, AKT phosphorylation, that induces apoptosis resistance and cell migration. It has been recently demonstrated that SphK1 is overexpressed in adrenocortical carcinoma (ACC) in comparison to adenomas (ACA) and that a high expression is related to worse outcome. Different SphK1 inhibitors...

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...

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)...

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...

Adrenocortical carcinoma (ACC) has heterogeneous prognosis and no effective targeted therapies. Pan-genomic studies identified complex molecular patterns related to outcome. Our study aimed at identification of an ‘easy-to-apply’ molecular signature for better personalized prognostic stratification. A total of 107 ACC patients were enrolled. Clinical/histopathological parameters of prognostic relevance were evaluated. Targeted molecular analysis was performed on DNA ...