Endocrine Abstracts

In human prostate, Oestrogen receptor α (ERα) expression in the epithelium increases with tumour Grade and promotes proliferation involving classical genomic and rapid non-genomic signalling, as well as transcription regulation of non-coding RNA. Similarly, in the tumour stroma there is up-regulation of ERα, corresponding with declining AR, resulting in a higher ratio of ERα:AR with increasing Grade. Additionally, in prostate cancer-associated fibroblasts (...

Patients with adrenal insufficiency require increased hydrocortisone (HC) replacement doses during surgery, trauma and infection to avoid life-threatening adrenal crisis. However, currently administered HC doses are chosen empirically rather than on rational grounds, with huge variability in administration modes, total dose and dosing intervals. To conclusively determine serum cortisol levels observed under stress conditions, we firstly collected blood samples from healthy con...

5α reductases 1 and 2 (SRD5A1 and SRD5A2) metabolise cortisol into inactive 5α-dihydrocortisol contributing to the regulation of cortisol availability in addition to their established role in the generation of dihydrotestosterone from testosterone. Dutasteride and finasteride are commonly prescribed to patients with benign prostatic hyperplasia but their potential metabolic effects have only recently been identified. Dutasteride inhibits both SRD5A1and SRD5A2 whilst ...

Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the commonest cause of liver cirrhosis and leading indication for liver transplant worldwide. It is tightly associated with obesity and type 2 diabetes, yet the precise mechanisms that drive its aetiology are not fully defined. Dysregulation of both glucocorticoid and androgen metabolism has been implicated in its pathogenesis. The availability of these hormones to bind and activate their receptors is mainly regulat...

Recently, liquid chromatography–tandem mass spectrometry (LC–MS/MS) was stated to be the method of choice to measure sex steroids.1 Information on the mutual agreement of LC–MS/MS methods, however, is scarce. Therefore, we compared seven published LC–MS/MS methods for the simultaneous measurement of testosterone, androstenedione, and DHEA. Fifty-five random serum samples obtained from volunteers were analysed in duplicate by seven published LC&#1...

Introduction: Definitive diagnosis of lymphocytic hypophisitis (LH) lacks a pathological analysis. The detection of pituitary antibodies (PAB) with the current methods presents variable results and its clinical utility is therefore limited. Recently, new methods were released for the interpretation of indirect immunofluorescence (IIF), which can increase the specificity for detection of PAB.Methods: We evaluated four patients followed in endocrinology co...

Introduction: Prostate cancer is hormone dependent and regulated by a balance of androgens as well as estrogens. Regulatory control is also exerted by the tumor microenvironment including cancer-associated fibroblasts (CAFs), and immune cells. Although patient derived xenografts (PDX) commonly used to study the functional effects of CAFs, the method is not quantitative, is lengthy, technically challenging and the xenografts are placed in immune suppressed hosts excluding immun...

Background: Thymus transplantation is undertaken for conditions associated with severe immunodeficiency. These comprise various genetic and syndromic associations including 22q deletion syndrome, CHARGE association, diabetic embryopathy, and other rarer conditions. Some of these conditions are associated with hypoparathyroidism and therefore hypocalcaemia. There are no established guidelines on the management and prevention of hypocalcaemia during the transplant period.<p ...

Patients with adrenal insufficiency (AI) require adjustment of hydrocortisone (HC) dose to avoid life-threatening adrenal crisis during illness, surgery and trauma. However, current dose recommendations are based on empirical grounds only and choice of dose and administration modes vary considerably. We designed the PACS study to compare cortisol levels achieved by currently recommended HC stress doses to those in i) healthy controls (n=85, 21–70 years), ii) mili...

Background: The treatment of metastatic castration-resistant prostate cancer (CRPC) remains dependent on Androgen Receptor (AR) mediated signalling, thus understanding all components involved in testosterone signalling in these men is of utmost importance. Recent studies have identified 11-ketotestosterone (11 KT) as a potent androgen receptor (AR) agonist present in humans. However, it is unknown if 11 KT is present at physiologically relevant concentrations in CRPC patients....