Endocrine Abstracts

Introduction/Background: Somatostatin analogue injections are a mainstay for the treatment of Neuroendocrine Tumours. Gallstones are a known adverse effect of this treatment. PRRT can bring extra complications for patients having an episode of cholecystitis, biliary colic, cholangitis or pancreatitis.Aims: To examine a cohort of patients undergoing PRRT, looking for the incidence of gallstones and how many patients suffe...

Introduction: The Birmingham Neuroendocrine Tumour (NET) and Carcinoid Heart Disease( CHD) services evolved into a combined and bespoke specialist service in 2018, with the introduction of the enhanced CHD pathway. This involved discussion at the CHD NET MDT , CHD work-up in the inpatient or outpatient setting and a clinical review in the bespoke CHD NET clinic. The CHD NET pathway is now embedded and well-established at our centre. We have a consistent flow o...

Whilst the majority of familial medullary thyroid cancer (MTC) is caused by germline mutations of the RET proto-oncogene, there are families and individuals with predisposition to MTC in whom no RET mutation has been identified (non-RET MTC). Recently, we identified novel mutations in a single gene termed MTC2 in non-RET MTC individuals by whole exome sequencing. The precise role of these MTC2 germline mutations in MTC tumorigenesis is however unclear. Here, we examined the fu...

Islet transplantation, an effective treatment for Type I Diabetes, is compromised by transient ischemia. Ischemia reduces the viability and function of transplanted islets and may also promote signals that lower islet efficacy. In order to characterize the response of human islets to transient ischemia, high-throughput sequencing was employed to determine global gene expression. Islets isolated from healthy donors (n=4) were either pelleted in microcentrifuge tubes (i...

PBF is a ubiquitous glycoprotein which is over-expressed particularly in endocrine and endocrine-related cancers. Previously classified as a proto-oncogene, 11 substitution-missense mutations of PBF have now been reported in tumours from patients with ovarian, prostate and colorectal cancers via the COSMIC database, suggesting PBF may in fact be an oncogene. We have therefore examined the biological implications of all 11 mutations. Substitution mutations, which occurred acros...

Introduction: Sphingosine-1-phosphate lyase (SGPL1) catalyses the final step in sphingolipid metabolism, irreversibly degrading the lipid signalling molecule sphingosine-1-phosphate (S1P). The relative abundance of S1P compared to its precursors sphingosine and ceramide finely tunes signal transduction for a wide range of cellular pathways including proliferation, apoptosis, migration and calcium handling. Loss-of-function mutations in SGPL1 cause a spectrum of disorders, incl...

Familial glucocorticoid deficiency (FGD) is characterised by isolated glucocorticoid deficiency with retention of normal mineralocorticoid production. FGD causing mutations in the MC2R accessory protein, MRAP, often occur at the canonical donor splice-site of intron 3, presumed to result in skipping of the first coding exon with unknown consequences at the protein level. DNA from three patients (0 - 6 months) with high ACTH and/or low cortisol levels underwent whole e...

Introduction: Enteroendocrine cells (EECs) are hormone-secreting cells within the intestinal epithelium that play an important role in regulating food absorption, insulin secretion and appetite. To understand the molecular mechanism governing the function of EECs, it is important to investigate cell-type-specific gene expression. The aim of this study was to identify the transcriptome of human EEC populations from organoid culture.Methods: To label the f...

Gestational diabetes (GDM) occurs when beta-cell insulin secretory capacity is insufficient to meet the increased demands required to maintain normoglycemia during pregnancy. Considerable clinical evidence supports a link between depression and GDM, although underlying mechanisms are unclear. We used the unpredictable chronic mild stress (UCMS) rodent model of depression to examine the metabolic effects of depression in pregnant mice. C57BL/6J females were divided at 4-weeks-o...

Background: Previous reports suggest that epilepsy and autism are more common in children with autoimmune diseases such as type 1 diabetes (T1D). While each condition is common in the general population, only small numbers of children have the two conditions together, so there is currently little coordinated support. We sought to describe the incidence in our own population.Methods: Retrospective review of the Diamond database and clinical notes for chil...