Endocrine Abstracts

Background: Pancreatic neuroendocrine tumors (panNETs) are heterogeneous, with grade (G) defined by Ki67 proliferation index (<3% G1, 3-20% G2, and >20% G3) or mitotic rate. Previous studies suggest that baseline Ki67 index may be confounded by biopsy site (primary or metastasis), biopsy technique and primary tumor size. Ki67 differences leading to grade discordance in PanNETs at baseline is relatively understudied. Our study aims to evaluate grade discordance in synch...

Various haemostatic abnormalities have been associated with thyroid dysfunction, especially with hypothyroidism. The underlying mechanisms are not well established.The aim of the study was to evaluate the primary and secondary haemostasis in patients with severe hypothyroidism, to assess the role of thyroid hormone deficiency and to determine whether increased serum TSH level despite normal free thyroid hormone concentrations could influence the coagulat...

Introduction: The destination of young people referred from the NHS Gender Identity Development Service (GIDS) to the two paediatric endocrine centres covering England and Wales has not been analysed previously.Methods: 1151 young people identifying as gender variant were referred from GIDS for an endocrine opinion: 827 patients to University College London Hospital (UCLH) from 2008; 324 to Leeds Children’s Hospital (LCH) from 2013. Outcomes were no...

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...

Background: Immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 and its ligand (PD-1/PD-L1) are the current standard-of-care for many advanced cancers (1). This novel therapeutic approach comes with its costs in the form of immune-related adverse events (irAE). The underlying mechanisms are not yet fully understood. We explore the role of HLA in endocrinopathy related to ICI therapy using an interes...

Introduction: Hyponatremia is the most common electrolyte disorder and the syndrome of inappropriate antidiuresis (SIAD) is one of its main causes. However, treatment options for chronic SIAD-induced hyponatremia are inadequate. This is problematic because hyponatremia has been associated with neurocognitive deficits, although there is little data on its reversibility. We previously showed that the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin is a promising s...

Background: The cyclic GMP-AMP synthase stimulator of interferon genes (cGAS-STING) signalling pathway is an element of the innate immune response and is activated by the presence of DNA in the cytosol. Triggering of this immune response may occur in the setting of infection or neoplasia. Activation of this pathway results in phosphorylation of interferon regulatory factor 3 and downstream transcription of cytokines such as interferon β and interleukin-6. Polyinosinic:pol...

CRN04894 is a potent, orally bioavailable nonpeptide that is a highly selective antagonist for melanocortin type 2 receptor (MC2R). This receptor is found exclusively in the adrenal cortex and is the primary mediator of adrenal activation. We report results from a randomized, double-blinded, placebo-controlled (6 active:3 placebo/cohort), multiple ascending dose (40, 60, and 80 mg) study in health volunteers evaluating safety, pharmacokinetics, and pharmacodynamics of oral, on...

Introduction: Primary aldosteronism (PA) is the most frequent form of secondary hypertension. Over the past 10 years, important discoveries have been made regarding the genetic basis of aldosterone producing adenoma and familial forms of primary aldosteronism. In most cases, genetic abnormalities are found in genes coding for ion channels (KCNJ5, CACNA1D, CACNA1H, CLCN2) and pumps (ATP1A1, ATP2B3). These mutations affect intracellular ion homeostasis and/or c...

A 70-year old man was referred to the endocrinology department for the evaluation of a pituitary macroadenoma which was diagnosed during work-up for a malignant melanoma. Pituitary MRI showed a 20×21×25 mm adenoma with supra-sellar extension and no compression of the optic chiasma. Hormonal work-up revealed central hypogonadism and slight hyperprolactinemia due to stalk compression, while pituitary function was otherwise normal. MRI follow-up was scheduled in six mon...