Endocrine Abstracts

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...

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...

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: There have been conflicting reports on fertility, reproduction rates and pregnancy outcomes in women with congenital adrenal hyperplasia (CAH). Identification of potential modifiable influential factors of pregnancy outcomes in these women has been hampered in the past by either small sample sizes or data derived from epidemiological samples.Methods: Retrospective multi-center study including a total number of 72 women with CAH (n=34...

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...

Previously, we identified seven mutations in the main catalytic subunit of protein kinase A (PKA Cα) to be responsible for cortisol-secreting adrenocortical adenomas (CPAs): L206R, L199_C200_insW, S213R_L212_K214insIILR, C200_GlyinsV, W197R, del244-248+E249Q, E32V. Here we performed a functional characterization of these mutants. Specifically, we evaluated the association between PKA regulatory and catalytic subunits using co-immunoprecipitation and PKA activity using a k...

Background: Adrenal masses are discovered in 5% of abdominal imaging scans. Work-up aims at exclusion of malignancy and hormone excess. However, estimates of these risks derive from retrospective studies only, mostly small and with significant selection bias.Methods: Prospective multi-centre study (2011–2016) in 14 centres (11 countries) of the European Network for the Study of Adrenal Tumours (ENSAT) with prospective consecutive enrolment of patien...

The cAMP signaling pathway plays a major role in the pathogenesis of cortisol-producing adrenocortical adenomas (CPA). In adrenocortical cells cAMP induces dramatic changes in cell morphology accompanied by actin cytoskeleton rearrangements that precede steroidogenesis, the causal relationship between these events being still undefined. In this study we investigated cAMP effects on cytoskeleton rearrangements and steroidogenic response in mouse (Y1) and human adrenocortical tu...

Background: Adrenal masses are discovered in 5% of cross-sectional abdominal imaging scans. Work-up aims at exclusion of malignancy and hormone excess. However, estimates of these risks presently derive from retrospective studies only, mostly small and with significant selection bias.Methods: Prospective multi-centre study (2011–2016) in 21 centres (17 countries) of the European Network for the Study of Adrenal Tumours (ENSAT) with consecutive enrol...