Endocrine Abstracts

Introduction: Polymorphisms of the glucocorticoid (NR3C1) and mineralocorticoid receptor (NR3C2) have been linked to the regulation of HPA-axis and to glucocorticoid sensitivity. We investigated whether NR3C1 and NR3C2 polymorphisms correlate with the occurence of adrenal crises (AC) in patients with primary adrenal insufficiency (PAI).Material and methods: We investigated 100 patients with PAI (70% women, mean age 51±15 years). DNA was extracted fr...

Available glucocorticoid (GC) replacement regimens in adrenal insufficiency (AI) only roughly correspond to physiological steroid profiles. Control of substitution quality is therefore difficult but significant, as even mild chronic over- or under-replacement may be clinically relevant. FKBP5 regulates GC receptor sensitivity by reducing its affinity to cortisol when bound to the receptor complex. FKBP5 methylation has been inversely correlated with cortisol levels both in hea...

Background: Potentially fatal adrenal crises (AC) still occur in educated patients with adrenal insufficiency (AI). Identifying predisposing factors is necessary for prevention in this patient population.Objectives: Investigating clinical and biochemical fingerprints of increased susceptibility to AC.Material and methods: Our study population included 260 patients with chronic AI, classified as high and low risk according to the fr...

Adrenocortical carcinoma (ACC) is a rare malignancy with heterogeneous but dismal prognosis and despite numerous efforts to improve patient care, effective treatment options are still lacking. ACC in vitro research faces for decades one major obstacle - the unavailability of different ACC cell line models. Here, we present a newly established human ACC cell line that was directly transferred to and now proliferates in cell culture. JIL-O cell line was derived from a p...

Introduction: Streptozotocin (SZ) is an active drug for the treatment of advanced adrenocortical carcinoma (ACC) in a minority of patients with an objective response rate of <10%. It has been reported that expression of glucose transporter-2 (GLUT-2) is essential for SZ to enter tumor cells and that high activity of O-6-methylguanine-DNA methyltransferase (MGMT) counteracts the alkylating effect of SZ. Therefore, we aimed to clarify the role of GLUT-2 and MGMT in the respo...

Introduction: Glucocorticoid (GC) replacement regimens in adrenal insufficiency (AI) only roughly correspond to physiological steroid profiles. Moreover, control of substitution quality is difficult and signs of clinically relevant mild chronic over- or under-replacement might be omitted. FKBP5 regulates GC receptor sensitivity by reducing its affinity to cortisol when bound to the receptor complex. FKBP5 methylation has been inversely correlated with cortisol levels both in h...

Context: Adrenocortical carcinoma (ACC) are endocrine malignant neoplasms associated with severe aggressiveness. By applying of ‘multiple omics’ approach, we recently categorized ACC patients based on their steroidogenic activity and expression of immune activation marker, which is along with prognosis; an ‘immune’ phenotype with good and a ‘steroid’ phenotype with bad outcome.Hypothesis: Our central hypothesis focuses on th...

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...

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...