Endocrine Abstracts

According to recent studies, primary aldosteronism is considered to be responsible for almost 10% of all cases of arterial hypertension. The genetic background of this common disease, however, has been elucidated only for the rare familial types whereas in the large majority of sporadic cases it still remains unclear. In an attempt to define novel genetic mechanisms of hyperaldosteronism we utilized a random mutagenesis screen after treatment with the alkylating agent N...

Tissue samples from adrenal tumors provide the basis for standard diagnostic procedures such as pathological examination. In addition, these tumor samples have been an invaluable source for the discovery of novel molecular pathways involved in adrenal tumorigenesis. Information on the molecular phenotype are based on DNA mutation analysis and epigenetic changes, RNA and protein expression pattern and sub-cellular localization as well as post transcriptional protein modificatio...

The tumorigenesis of Cushing’s disease is characterized by somatic mutations in the USP8 gene in almost half of the cases. USP8 encodes for ubiquitin specific protease 8, a deubiquitinase that rescues proteins involved in the regulation of ACTH synthesis in corticotroph cells. In the present study we tested the antisecretory and antiproliferative efficacy of a commercially available specific USP8 inhibitor (IC50 3.1 μM USP8; >90 μM USP7) in immortalized muri...

Introduction: Transcriptional regulation of gene expression by miRNAs is critical for the fine-tuning of adrenal stress response. However, its role in hypercortisolism has not been explored well. The study addresses this gap using adrenal samples of 3 patient groups from the German Cushing’s registry: Cortisol-Producing-Adenoma (CPA), Primary Bilateral Adrenal Hyperplasia (PBMAH) and controls (adrenal samples of patients with pheochromocytoma).Metho...

Background: Symptoms of hyperandrogenism are common in patients with Cushing’s disease (CD), but they cannot be sufficiently explained by measured concentrations of circulating androgens. In this study we analyzed the contribution of 11-oxygenated (11o×C19) androgens to hyperandrogenemia in female patients with CD as well as the influence of treatment with steroidogenesis inhibitors osilodrostat and metyrapone on 11o×C19 and classic androgens.<p class="abste...

Introduction: Transcriptional regulation of gene expression by miRNAs is critical for the fine-tuning of stress response. However, its role in hypercortisolism has not been explored well. After exploring circulating miRNAs in Cushing’ Syndrome (CS) as biomarkers our aim was to investigate their origin and their role in adrenal tissue.Methods: Next generation sequencing (NGS) based miRNA profiling was performed in adrenal samples from patients of Ger...

Background: Endogenous Cushing’s syndrome (CS) is associated with increased susceptibility to infections and mortality. Previously reported effects of hypercortisolism on immune function include a reduced CD4+/CD8+ ratio with a shift towards IL4+T helper cells (Th2), suppressed NK-cell cytotoxic activity as well as a low-grade inflammatory profile.Aim: This cross-sectional single center study aims to compare immune phenotype in patients with overt C...

Poor agreement between different analytical methods measuring aldosterone concentrations impedes applicability of uniform cut-offs in the diagnostic work-up of primary aldosteronism (PA). We compared 4 analytical methods (2 immunoassays and 2 LC-MS/MS) in plasma samples before and after saline infusion test (SIT). 80 hypertensive patients underwent the standardized diagnostic work-up within the German Conn’s registry. Patients (PA n=39/non-PA n=41) were ...

Background: Primary aldosteronism is commonly caused by an aldosterone-producing adenoma (APA). Somatic mutations in the KCNJ5 gene (encoding an inwardly rectifying potassium channel) are found in around 40% of APAs, KCNJ5 germline mutations cause familial hyperaldosteronism type III. The role of KCNJ5 mutations in excessive aldosterone production is established but their role in cell growth is unclear.Objective: To study the e...

The prolonged exposure to an excess of circulating cortisol (Cushing’s syndrome) causes various complications. An accurate and early diagnosis is critical for effective surgical management and optimal prognosis. However, the current diagnostic approach based on hormonal assays can be complex and requires multiple tests. The identification of novel, specific and easily measurable biomarkers of hypercortisolism may help to improve the diagnosis and to evaluate the complicat...