Endocrine Abstracts

Estrogen Receptor alpha (ER) is the key driver in the majority of all breast cancers, and considered the main target for therapy. However, resistance to treatment is common and biomarkers to facilitate optimal treatment selection are urgently needed. Even though the vast majority of breast cancer patients are female, breast cancer can develop in men as well. Using chromatin immunoprecipitation followed by massive-parallel sequencing (ChIP-seq), we identified the genome-wide ch...

Background: Alström Syndrome (AS) is a rare autosomal recessive disease featuring highly accelerated insulin resistance, fatty liver, diabetes and heart failure among other syndromic features. Heart failure leads to significant early mortality, but is complex and likely multifactorial, with developmental defects, accelerated atherosclerosis, and fibrosis all implicated. These cardiometabolic complications occur in the face of only moderate obesity in many patients. AS is ...

Objectives: Mutations in the DICER1 gene represent driver events in development of pediatric thyroid nodules, malignant as well as benign. The occurrence of these mutations has been reported in differentiated thyroid carcinomas, poorly differentiated thyroid carcinomas, non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), multinodular goiters and follicular adenomas. The aim of this study was to detect mutations in DICER1 g...

Introduction: Hormone-producing pituitary cell lineages derive from SOX2+ embryonic precursors. These cells maintain multipotency into early postnatal life, acting as the resident population of pituitary stem cells (PSCs) and contributing extensively to all the endocrine cell lineages. Additionally, paracrine signalling from PSCs is important for cell proliferation of neighbouring progenitors (PMC7803373). It is not known if SOX2+ PSCs are involved in the regulation of additio...

Background: Previous studies have shown an association between low CYP11B2 DNA methylation levels and high CYP11B2 mRNA levels in aldosterone-producing adenoma (APA), suggesting that epigenetic mechanisms play a pivotal role for regulating CYP11B2 function in primary aldosteronism. It has been proposed that aldosterone-producing cell clusters (APCCs) may become a source of autonomous aldosterone production when evolving into APA.Aim: Our aim was to deter...

Background: TMEM127 encodes for a ubiquitously expressed transmembrane protein with limited knowledge into its role. TMEM127 germline loss-of-function is a driver of pheochromocytoma and paraganglioma (PPGLs), tumors derived from the adrenal medulla and extra-adrenal paraganglia, respectively. Molecularly, TMEM127 mutant PPGLs belong to the kinase cluster, characterized by kinase signaling transcriptional programs. Receptor tyrosine kinase RET, a driver of PPGLs via germline o...

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell-clusters of normal adrenals could suggest the existence of co-driver mutations which influence the development or phenotype of APAs [1]. Gain-of-function mutations in both CTNNB1 and the G-protein coupled receptor GNA11 were found by whole exome sequencing in 3/10 APAs. Further sequencing of...

Gonadotroph tumours (GoTs) are frequent intracranial neoplasms that represent 30% of all pituitary tumours (PiTs). While GoTs are responsible of an important morbidity, their tumorigenesis is not yet understood, and their treatment is limited to surgical resection and radiotherapy. The absence of identified driver-genes combined with their heterogeneity and silent behaviour (i.e. lack of hormone hypersecretion) limit the development of medical treatment. The current lack of re...

Background: Pheochromocytoma (Pheo) is a tumor deriving from chromaffin cells. It can be studied using 18F-dihydroxyphenylalanine (DOPA) - positron emission tomography (PET) due to its overexpression of L-type amino acid transporters (LAT1 and LAT2). The oncogenic pathways involved are still poorly understood. This study examined the relationship between 18F-DOPA-PET uptake and LAT1 expression, and explored the role of miR-375 and putative target genes.</...

Introduction: The NPDA presents data on management, treatment, and complications for all diabetes units in the country. This acts as a driver for quality improvement and aims to improve standards of diabetes care. The 2019 report identified a relatively high proportion of children with hypertension locally. An audit aimed to identify the proportion of local diabetes patients with ‘hypertension’ or ‘pre-hypertension’, and their clinical identification. The s...