Endocrine Abstracts

Pheochromocytoma is a rare disease but frequently poses a diagnostic dilemma due to the unspecific symptoms and its potentially life-threatening nature. There is a perception of an increase in the incidence of pheocromocytomas in recent years, but no data on time trends exist. We obtained data from The Danish National Registry of Patients, The Danish Registry of Causes of Death, and The National Pathology Registry for all persons registered with pheochromocytoma in 1977–2...

Genomics England with the consent of participants and the support of the public is creating a lasting legacy for patients, the NHS and the UK economy, through the sequencing of 100,000 genomes. 50,000 genomes from cancer, two per patient (tumour and a paired blood sample) and 50,000 from rare disease, three genomes per patient (affected person plus two blood relatives). The main project started sample collection in March 2015, aiming to collect samples by the end of 2017 throu...

Nocturnal salivary cortisol (NSC), urinary free cortisol (UFC) and overnight dexamethasone suppression testing (ODS) are recommended screening tests for Cushing’s syndrome (CS). Individual centers differ in their screening approach; UFC being the test of choice in Northern Ireland with ODS in patients with adrenal incidentalomas. NSC, which measures free cortisol, is not routinely used. The aims of this study were to 1. Evaluate the utility of NSC in the diagnosis of CS; ...

We previously demonstrated that USP12 functions as an AR co-activator by directly deubiquitinating the AR and stabilising its protein levels. Additionally, we showed that USP12 targets the PHLPP AKT phosphatases leading to decreased levels of activated, phosphorylated AKT (pAKT) and as such indirectly stabilises the AR preventing its phosphorylation at serine 213. We further investigated the role of USP12 in prostate cancer by analysing the transcriptome of the LNCaP prostate ...

Prostate cancer (PC) growth is androgen-dependent, hence, the mainstay for treatment is hormone-ablation therapy using anti-androgens, and/or androgen-deprivation therapies. Unfortunately, after a median time of 18 months, the cancer reappears in an androgen independent form, termed castrate-resistant PC (CRPC), which is largely fatal. To date, many molecular mechanisms have been suggested to be responsible for persistent AR signalling in CRPC. AR variants (AR-Vs), short forms...

Phosphorylation of the Androgen Receptor (AR), has been shown to play an important role in directly modulating AR activity. However, the full extent of which protein kinases are involved in the regulation of the AR remains unknown. In order to address which kinases are important in the regulation of AR activity in both androgen sensitive and independent prostate cancer (PCa), a comprehensive siRNA kinome screen was performed. AR transcriptional regulation was evaluated using a...

Prostate cancer (PC) is currently the most commonly diagnosed non-cutaneous cancer affecting UK men. Androgen deprivation therapy (ADT) has traditionally been used as the gold standard treatment for advanced PC. Despite the initial response to androgen ablation, tumours relapse and become refractory to clinically approved anti-androgens, resulting in castration-resistant PC (CRPC). In CRPC, androgen receptor (AR) signalling is inappropriately restored by AR splice variants (AR...

Although new treatments for castrate-resistant prostate cancer (CRPC), such as enzalutamide and abiraterone, have shown promise, moderate response rates and development of resistance to these agents has limited their clinical effectiveness. It is therefore vital we improve our understanding of androgen receptor (AR) re-activation in advanced disease, focusing particularly on regulatory processes governing activity of AR mutants and splice variants (AR-Vs), to enable the develo...

The relation between androgen receptor (AR) gene amplification and other mechanisms behind castration-resistance in prostate cancer, such as increased expression of constitutively active AR variants and steroid-converting enzymes have been poorly examined. Specific aims of this study were to examine AR amplification in treatment-naïve and castration-resistant prostate cancer (CRPC) bone metastases and to explore molecular and functional differences. AR gene amplification ...

Background and aims: Rickets is a childhood condition resulting from impaired mineralisation of the growth plate, resulting in bony deformities. A retrospective survey was undertaken to identify causes of rickets in children treated at the Royal Manchester Children’s Hospital from 2009 to 2014.Methods: Cases of rickets were identified through a search of all paediatric radiology reports containing the words ‘Rickets’ or ‘Osteomalacia&...