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...

Background: Potentially fatal adrenal crises (AC) still occur in educated patients with adrenal insufficiency (AI). Our study investigates clinical and biochemical fingerprints of increased susceptibility to AC.Material and methods: 199 patients with chronic AI (disease duration ≥6 years), classified into tertiles according to the frequency of AC/patient-years (group 1 no AC, group 2 ≤0.07 AC/py, group 3 >0.07 AC/py). Following parameters...

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...

Introduction: Methylation of FKBP5, a glucocorticoid(GC)-receptor co-chaperone, negatively correlates with cortisol levels in both healthy and hypercortisolaemic individuals, and may serve as an indicator of GC exposure. We explored whether GC replacement correlates with FKBP5 methylation levels in patients with adrenal insufficiency (AI), aiming to assess the adequacy of substitution therapy.Methods: In 122 patients with chronic primary (n=73) ...