Endocrine Abstracts

Background: The lack of relevant in-vivo and in-vitro models has precluded investigations of the pathophysiology of metastatic NENs. Organotypic tumour slices retain the complexity of tumours in-vivo without extensive manipulation of the tissue. The aims of this study are to understand the utility of precision cut slice technology to develop an immunocompetent model of metastatic GEP NENs to test new therapeutics and elucidate immunological, molecula...

Introduction: Primary aldosteronism (PA) is mainly caused by unilateral aldosterone-producing adenomas (APA) or bilateral adrenal hyperplasia (BAH). Subtype differentiation relies on the invasive and technically challenging adrenal venous sampling (AVS). We recently demonstrated the potential utility of peripheral plasma steroid profiling by LC-MS/MS to distinguish APA and BAH. We tested the following hypotheses: first, if steroid profiling in combination with AVS, effectively...

Rationale: Endothelial dysfunction (ED) is a hallmark of primary aldosteronism and paves the way for subsequent atherosclerotic disease. Past research has confirmed that one factor involved in ED is disturbed nitric oxide (NO) signalling. Since defects in NO release alone cannot explain the whole effect, we set out to address the role of endothelial CYP-expoygenase products (epoxyeicosatrienoic acids, EETs) in aldosterone-mediated endothelial dysfunction.<p class="abstext"...

Endocrine cells utilise endocytosis to scavenge polypeptide hormones, and to generate signals from inactive precursors, such as release of thyroid hormones from thyroglobulin in thyrocytes, and activation of vitamin D after reabsorption of ultrafiltrated pro-vitamin D binding protein complex by renal proximal tubular cells (PTC). We have investigated the role of CLC-5, a chloride/proton antiporter expressed in apical endosomes and the apical plasma membrane of thyrocytes and P...

Accumulating evidence suggests that the immunological landscape plays a key role in the progression of neuroendocrine liver metastases (LM-NENs), which is often characterised by immune cell infiltration. Anti-tumour functions of infiltrating lymphocytes are often silenced through hyper-expression of inhibitory checkpoint receptors (CRs) such as PD-1, but favourable outcomes with anti-PD-1 therapy have been low. Recently, functional soluble (cell-free) CRs beyond PD-1 have been...

Background: Primary aldosteronism (PA) is the most common potentially curable cause of secondary hypertension and is a risk factor for cardiovascular morbidity and mortality. For patients with unilateral disease adrenalectomy can be curative. However, PA remains substantially underdiagnosed due the complex diagnostic pathway required to identify patients with unilateral disease, and the difficulties in accurate lateralization of the affected adrenal gland. Spe...

X-linked IGSF1 (immunoglobulin superfamily, member 1) loss-of-function mutations in males are associated with central hypothyroidism, macroorchidism, and a variable spectrum of anterior pituitary dysfunction. Igsf1 deficient male mice also exhibit central hypothyroidism, however, the physiological and molecular function of IGSF1 in both species has not yet been elucidated. Although partial transient GH deficiency is a ra...

X-linked IGSF1 (immunoglobulin superfamily, member 1) loss-of-function mutations in males are associated with central hypothyroidism, macroorchidism, and a variable spectrum of anterior pituitary dysfunction. Igsf1 deficient male mice also exhibit central hypothyroidism, however, the physiological and molecular function of IGSF1 in both species has not yet been elucidated. Although partial transient GH deficiency is a ra...

Background: Silver Russell syndrome (SRS) is genetically heterogenous and around 30% of patients with clinical SRS have no genetic diagnosis. Point mutations in HMGA2 have been reported in 4 patients worldwide causing growth failure and an SRS-like phenotype. Despite strong evidence of the crucial role of HMGA2 in growth across species, the mechanism of action of HMGA2 in human linear growth is unclear.Objective: Identify and f...

Primary Aldosteronism (PA) is the most frequent cause of endocrine hypertension. Three forms of familial hyperaldosteronism (FH) have been described, named FH-I to -III. Recently, a mutation of KCNJ5 has been shown to be associated with FH-III, whereas the cause of FH-II is still unknown. In this study we searched for mutations in KCNJ5 in 46 patients from 21 families with FH, in which FH-I was excluded. We identified a new germline G151E mutation in two PA affected subjects f...