Endocrine Abstracts

Polycystic ovary syndrome (PCOS) affects 10% of women and is associated with an increased risk of type 2 diabetes and fatty liver disease. Androgen excess is an important driver of metabolic risk in PCOS. In adipose tissue from women with PCOS, increased activation of androstenedione (A4) to testosterone (T) by the enzyme AKR1C3 results in systemic lipotoxicity. Recent in-vitro studies also demonstrated that T and 11-ketotestosterone (11KT) activate the androgen recep...

Aims: Prolyl-4 hydroxylase domain protein 3 (PHD3) is an alpha ketoglutarate-dependent dioxygenase involved in the oxygen-dependent regulation of cell phenotype. While PHD3 has been reported to suppress insulin sensitivity in the liver, little is known about effects of the enzyme in insulin-secreting β-cells.Methods: βPHD3−/− mice were generated by crossing the Ins1Cre driver line with animals bearing a floxed Egln3</...

Efnb2 encodes for the ligand Ephrinb2 that binds to its cognate Eph receptor, with which plays an integral role in angiogenesis, stem cell regulation and tumorigenesis. Using a pituitary-specific Cre-driver (Hesx1Cre), we conditionally deleted Efnb2 from the early stem/progenitor cells (PSCs) of the developing pituitary gland. We found that Efnb2 is expressed in PSCs both during embryogenesis and adulthood, suggesting its...

A 38 year old female was identified as carrying a heterozygous pathogenic MEN1 variant (c.13404delG) through predictive testing, following a diagnosis of familial hyperparathyroidism. Routine screening for hyperparathyroidism and pituitary disease was negative. However, a CT thorax-abdomen-pelvis revealed a 41 mm pancreatic tail mass. Biopsy via endoscopic ultrasound confirmed a well-differentiated (grade 1) pancreatic neuroendocrine tumour (pNET) with MIB1<1%. Bi...

Background: A normal islet includes both mature and immature β-cells, with the former possessing higher insulin content and the latter displaying better proliferative capacity. However, it remains unknown whether immature β-cells also contribute to the regulation of insulin release, especially by commanding the activity of their mature counterparts.Materials and methods: Pdx1, Mafa, and Ngn3 were overexpressed in &#94...

Objectives: Coexistence of two different malignancies is frequently reported. Sometimes occurs in the context of well-established syndromes like MEN2. Rearranged during transfection (RET), is an oncogenic driver activated in different kinds of neoplasias such as: MTC, Differentiated Thyroid Cancer (DTC), Non-Small Cell Lung Cancer (NSCLC). We have previously reported an increased prevalence of DTC in familial MTC patients carrying the RET (G533C) mutation. Ai...

Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors derived from chromaffin cells of the adrenal medulla and paraganglia of the autonomic nervous system, respectively. Despite a common origin, these tumors are quite heterogeneous in terms of driver mutations, copy number alterations and activated downstream-signaling pathways. Genome wide expression analysis has identified at least three main tumor clusters: a pseudo-hypoxic cluster, one with activation ...

Introduction: CYP11B2 is a key enzyme of primary aldosteronism, and several factors are involved in the regulation of CYP11B2 expression and the overproduction of aldosterone. Somatic mutations in aldosterone-driver genes are strongly associated with CYP11B2 expression and have been only detected in the CYP11B2-positive tumor area, indicating that aldosterone producing adenoma (APA) intratumoral heterogeneity corresponds to non-uniform CYP11B2 expression in neoplastic cells. I...

The immune system has been recognized as one of the most important regulators of bone turnover and its de-regulation is implicated in several bone diseases as post-menopausal osteoporosis and inflammatory bone loss. The study of the relationship between immune system and bone metabolism is generally indicated under the term ‘osteoimmunology’, the vast majority of these studies have been performed in animal models, however several data have been confirmed also in huma...

Adrenal aldosterone excess is the most common cause of secondary hypertension and is associated with increased cardiovascular morbidity and mortality. However, adverse metabolic risk in primary aldosteronism extends beyond hypertension, with increased rates of insulin resistance, type 2 diabetes, and osteoporosis, which cannot be easily explained by aldosterone excess but would rather be associated with oversecretion of glucocorticoids. Over the last years, exome sequencing ha...