Endocrine Abstracts

In adult mice the adrenal cortex is divided, in two distinct functional zones, outermost zona glomerulosa (ZG) and innermost zona fasciculata (ZF), encapsulated by a thin layer of mesenchymal cells (capsule). The adrenal cortex undergoes constant centripetal cell renewal, reliying on recruitment of progenitors located within an outer cortex niche. Progenitors initially differentiate as ZG cells and undergo lineage conversion to ZF as they move within the cortex. This relies on...

Recurrent somatic mutations in KCNJ5, CACNA1D, ATP1A1 and ATP2B3 have been identified in aldosterone producing adenoma (APA). Although the role of these mutations in regulating aldosterone biosynthesis has been clearly established, the mechanisms involved in proliferation and APA formation still remain to be elucidated. The aim of our study was to identify pathways involved in adrenal cortex nodulation and APA formation.Transcriptomic a...

Primary aldosteronism is the most common form of secondary hypertension. Somatic mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D have been described in 50% of aldosterone producing adenomas (APA). To identify genetic alterations in new genes, we performed whole exome sequencing in 23 patients with APA negative for recurrent mutations in known driver genes. A low number of somatic variations were identified per patient, ranging from 1 to 22. N...

PCOS is associated with increased androgens, elevated insulin and obesity. As obesity and androgens promote insulin resistance and hyperinsulinemia increases ovarian androgen production, and the likelihood of obesity, the interaction between these factors is complex. We investigated the development of insulin resistance, hyperandrogenism and obesity using a clinically realistic ovine model of PCOS. Exposure of the pregnant ewe to increased testosterone from d62 to d102 of gest...

Recent pan-genomic analyses of tumor DNA identified specific patterns of DNA methylation –e.g. CpG islands hypermethylation in the promoter regions of genes- as pejorative prognostic markers in adrenocortical cancer (ACC). Integrated genomics clearly shows that ACC with such an hypermethylation belongs to specific subgroups of ACC with increased driver genes alterations and a poor survival.Aim: To confirm the prognostic value of this methylation pat...

Pancreatic neuroendocrine tumours (PanNETs) are clinically challenging diseases as they display variable outcomes. We performed genome sequencing on 100 sporadic, primary pancreatic neuroendocrine tumours (PanNETs) and defined the underlying mutagenic mechanisms and mutations promoting this rare malignancy. Genome-wide analysis showed PanNETs to have a lower mutation burden and greater genomic stability than pancreatic exocrine cancers. The most common mutational signatures we...

Background: Diabetes is a metabolic disorder characterized by chronic hyperglycaemia as a result of defective insulin secretion, insulin action or a combination. Poor glycaemic control increases the risk of microvascular and macrovascular complications. For group two driving license holders with diabetes there are specific requirements set out by the Driver and Vehicle Licensing Agency. It is therefore hypothesised that this patient group is likely to aim for less tight glycae...

The advent of new genetic techniques that allow for high-throughput sequencing in surgical tumour tissues and germline DNA has boosted progress in many fields of biomedical research. The technique has been proven to be particularly fruitful in the area of endocrine tumours with many new driver genes being identified over the last few years that are involved in cell growth but more importantly in hormonal autonomy. Examples account for aldosterone producing adrenal adenomas, in...

Adipose tissue (AT) dysfunction is thought to be a central component in the pathophysiology of obesity-associated metabolic disease. Low AT oxygenation (hypoxia) is suggested to be a driver of this dysfunction, yet studies in humans have resulted in conflicting data. Therefore, we aimed to investigate if markers of AT hypoxia were present in the subcutaneous AT of morbidly obese individuals who had hypoxia from obesity hypoventilation syndrome (OHS), with or without obstructiv...

Introduction: Hypogonadism is prevalent in older men and associated with various comorbidities. Despite this, it is underdiagnosed and undertreated.Aim: To identify factors associated with underdiagnosis and undertreatment of male hypogonadism.Methods: Quantitative, questionnaire-based, online survey conducted in the UK among men aged ≧40 years with hypogonadism confirmed by blood test (n=101, from N=3 871 ...