Endocrine Abstracts

Introduction: The age of onset and severity of thyroid disease in MEN2 kindreds can be variable, resulting in wide intrafamilial heterogeneity, despite the same oncogenic driver RET pathogenic variant being present. Our study sought to investigate the RET kinomic landscape in MEN2 to discover new biomarkers and to provide further mechanistic insights into malignant disease progression, focussing on paediatric cases.Metho...

Background and Aims: Obesity is a major risk factor for type 2 diabetes (T2D). Remission of diabetes can be achieved by dietary weight loss although the underlying molecular mechanism(s) are unknown. These beneficial effects could be related to decreasing hepatic fat delivery to the pancreas and eventually restoring β-cell function. We hypothesised that hepatic de novo lipogenesis (DNL) is the primary driver of pancreas “lipotoxicity” and the pr...

Impaired adipose tissue remodeling has been suggested as a pathophysiological driver of endocrinometabolic events in PCOS models, a condition that affects 6-21% of reproductive-aged women worldwide. Mitochondrial dysfunction, especially in the adipocyte plays a key role in adipose tissue inflammation that possibly aggravates endocrine/metabolic phenotypes in PCOS. Studies have reported Short-chain-fatty acids (SCFAs) as metabolic modulators that potentiate energy homeostasis. ...

The ret proto-oncogene (RET) encodes a transmembrane tyrosine kinase receptor of growth factors belonging to the glial-derived neurotrophic family, essential for the normal development of the kidneys, ureters, peripheral and enteric nervous system. Pathogenic variants in the RET gene result in multiple different phenotypes, which can range from isolated pathologies to multi-system disease, as a result of both loss and gain of RET function. Missense gain of function pathogenic ...

The RET receptor tyrosine kinase is an established oncogenic driver in multiple cancers. Activating RET point mutations give rise to the cancer syndrome Multiple Endocrine Neoplasia type 2 (MEN2), characterized by medullary thyroid carcinoma and pheochromocytoma. Correlations of specific RET mutations with MEN2 disease phenotypes and severity have been well documented, however the molecular mechanisms that distinguish the functions, locations, and protein interactions of speci...

Adrenocortical carcinoma (ACC) is a rare aggressive cancer with heterogeneous behaviour. Disease surveillance relies on frequent imaging, which comes with significant radiation exposure. Here we investigated the role of circulating cell-free DNA (ccfDNA) in ACC monitoring. We extracted ccfDNA from 1-4 ml EDTA-plasma using the Nonacus Cell3TMXtract or the Qiagen QIAamp MinElute kit and quantified by fluorimeter. We investigated 63 patients with ACC (25M/38F, 52±...

Case history: A 26 year-old lady was admitted from clinic with severe hypertension and bilateral papilloedema. Six weeks prior to admission she had undergone resection of a massive right upper quadrant lesion that was felt to be of hepatic origin. Histological analysis of the lesion revealed it to be an adrenal phaeochromocytoma and she was thus referred to the endocrine service. Pre-operative biochemical assessment had not been performed but there was no evidence of any blood...

Androgens initially drive prostate tumour growth. Although in advanced disease there is no longer dependence on circulating androgens, the androgen receptor (AR) remains a key driver of this lethal stage thus new ways to inhibit its activity are required. MicroRNAs play vital roles in prostate cancer (PCa) development, progression and metastasis. Previous studies have examined microRNAs dysregulated in PCa, and also identified androgen-regulated microRNAs. We approached microR...

It has long been known that the AR is regulated not only by its cognate steroid hormone, but also by interactions with a constellation of co-regulatory and signaling molecules. Checkpoint kinase 2 (CHK2) is a serine/threonine protein kinase whose main function is regulating the DNA damage response (DDR) triggered by double-strand DNA breaks. The androgen receptor (AR) is a major driver of prostate cancer, even at the castration–resistant stage of the disease. Our research...

Context: Primary bilateral macronodular adrenal hyperplasia (PBMAH) with glucose-dependent insulinotropic polypeptide (GIP)-dependent Cushing’s syndrome is caused by ectopic expression of GIP receptor in the adrenal tissue. The bilateral nature of this adrenal disease suggests germline genetic predisposition. We aimed to identify the molecular driver event responsible for ectopic GIP receptor expression in PBMAH.Methods: We conducted an internationa...