Endocrine Abstracts

Background: Immune checkpoint therapy response rate in adrenocortical carcinoma (ACC) is only ~15%. Glucocorticoid (GC) secretion is present in ~60% of tumours, associated with adverse outcome and has been associated with an immunologically cold tumoural microenvironment. On the other hand, activation of the Wnt/ß-Catenin pathway has been suggested to contribute to reduced immune infiltration.Aims: First, we aim to improve the understanding of cellu...

Prostate Cancer (PC) affects 1-in-6 men in the UK, and obesity 1-in-3, with rates of both increasing. High-fat diet is linked with increased risk of PC death, and volume of peri-prostatic adipose tissue (PPAT) is associated with increased risk of lethal PC/reduced therapy response. Despite this, molecular mechanisms underpinning obesity-driven PC remain poorly-understood. This is important since weight-gain and central obesity are major side-effects of PC trea...

Background: In mammalian cells, poly(ADP-ribose) polymerase-1 (PARP1) is among the earliest proteins to reach the site of DNA damage and play key roles in different cellular responses ranging from DNA repair to cell death. PARP-inhibitors are recommended in mono or combination therapy for a subset of breast and ovarian cancers with BRCAness type of DNA repair deficiency. In addition, current clinical trials are examining whether PARP-inhibitors can potentiate the efficacy of c...

Background: Pituitary neuroendocrine tumors (PitNETs) exhibiting treatment-refractory behavior are the rare subset that progress after radiation and are characterized by unrelenting growth and metastatic dissemination.Methods: To identify biomarkers of treatment-refractory behavior, two groups of patients with PitNETs were consented to matched tumor-normal whole exome and targeted next-generation DNA sequencing on a clinical protocol: a prospective group...

Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy that produces glucocorticoids in 60% of cases causing clinically relevant hypercortisolism. Since, we observed in another study, that shaping these immunosuppressive and life-threatining properties with corticosteroid inhibitors not only led to a glucocorticoid receptor-related downregulation of ROR1 but also to the upregulation of another promising membrane bound oncogenic antigen* (AG), we sought to...

Objectives: Free thyroxine (fT4) measurements are performed to detect thyroid disorders and monitor treatment. FT4 is measured using automated immunoassays (IAs) which face established analytical challenges due to low serum concentrations in the picomolar range and the precarious equilibrium between free and bound T4 (to thyroid-binding globulin (TBG) and (pre-)albumin). Furthermore, IAs are known to be affected by the composition of the serum sample (matrix-effects), which ca...

Bone metabolism in men is in part determined by sex steroid exposure. This is especially clear during puberty and senescence but it remains to be established whether declines in sex steroid levels during young and middle adulthood associate with changes in bone mass and size. This study investigated changes in bone mineral content (BMC), areal and volumetric bone density (aBMD; vBMD) and bone size in relation to sex steroid levels in 999 young adult men (age 24- 46 years) of w...

Introduction: Metastatic insulinoma is an extremely rare form of malignant insulinoma involving metastatic growth where classical surgical treatment is often impossible. Medical therapies are widely considered and reserved for those especially with inoperable insulinoma with the goals of reducing tumor size, but also of reducing hypoglycemic events either by acting directly on the insulinoma cells (reducing excess insulin secretion from the insulinoma cells or reducing tumor v...

Background: Fibroblast growth factor-21 (FGF21), which has recently been identified as a central regulator of metabolism, is known to be increased in conditions of obesity, insulin resistance, and fatty liver. Likewise, there is evidence that FGF21 increases with systemic inflammation. The aim of this study was to evaluate whether chronic low-grade inflammation might be the underlying mechanism and whether an anti-inflammatory treatment decreases FGF21 levels in metabolic diso...

Background: Canonical Wnt-signalling is important for bone by regulating osteoblastogenesis and osteoblast function. Bone metabolism is also partly determined by sex steroid exposure and sex differences in serum sclerostin levels have been reported. However, it is unclear whether serum sclerostin and other circulating Wnt-signalling components are sex steroid dependent within healthy men.Objective: To determine whether serum sclerostin, osteoprotegerin (...